Quinazoline derivatives having tyrosine kinase inhibitory activity

ABSTRACT

A compound which inhibits both of EGF receptor tyrosine kinase and HER2 tyrosine kinase is provided. 
     A compound represented by the general formula (I): 
                         
wherein R X  is a group represented by the formula:
 
                         
wherein R 1  is a hydrogen atom, optionally substituted alkyl, etc.; Z is —O—, —N(R 10 )—, etc.; R 10  is a hydrogen atom, alkyl, etc.; R 2  is a hydrogen atom, optionally substituted alkyl, etc.; R 18  is a hydrogen atom, optionally substituted alkyl, etc.; R 19  is optionally substituted alkyl, etc.; W 1  is an optionally substituted non-aromatic nitrogen-containing group; R 17  is a hydrogen atom, optionally substituted alkyl, etc.; R 3  and R 4  are independently a hydrogen atom, optionally substituted alkyl, etc.; X is —O—, —S—, or —N(R 12 )—, etc.; R 12  is a hydrogen atom, alkyl, etc.; and A is phenyl optionally having a substituent, etc.,
 
its pharmaceutically acceptable salt, or a solvate thereof.

This application is a Continuation of U.S. Ser. No. 11/884,819 filedNov. 1, 2007, which is a National Stage Application ofPCT/JP2006/303125, filed Feb. 22, 2006, which applications areincorporated herein by reference.

TECHNICAL FIELD

The present invention relates to a compound which inhibits both of EGFreceptor tyrosine kinase and HER2 tyrosine kinase, and a pharmaceuticalcomposition containing it as an active ingredient.

BACKGROUND ART

Tyrosine kinase is an enzyme which phosphorylates tyrosine residues insubstrate proteins, and is known to play an important role in anintracellular signal transduction system concerning cellulardifferentiation and proliferation. Two receptor tyrosine kinases, EGFreceptor (hereinafter EGFR) and HER2 (also called ErbB2 or Neu) areconsiderably involved in cancer development, and their activities areincreased in a variety of human cancers (Non-Patent Literature 1,Non-Patent Literature 2 and Non-Patent Literature 3). It is also shownthat these kinases are aberrantly expressed in cancers of brain, lung,stomach, intestine, pancreas, head and neck part, esophagus, bladder,kidney, prostate, ovary, breast, uterine, and thyroid gland (Non-PatentLiterature 4 and Patent Literature 1). Therefore, it is thought that aninhibitor of these kinases is useful as an anti-cancer drug which can beefficacious in many types of cancers and has little side effect. As thetyrosine kinase inhibitor, compounds described in Patent Literature 2,Patent Literature 3, Patent Literature 4, Patent Literature 5, PatentLiterature 6, Patent Literature 7 are known.

In addition, it is known that cellular transformation due to EGFR isaccelerated by additional coexpression of HER2 (Non-Patent Literature5). Further, concomitant expression of EGFR and HER2 is reported as amarker of poor prognosis in breast, oral cavity and lung cancers(Non-Patent Literature 6). As a drug which inhibits both EGFR and HER2,compounds described in Patent Literature 8 are known.

An anti-cancer agent having an oxime-type substituent at a 4-position ofa quinazoline derivative is described in Patent Literature 9 and PatentLiterature 10.

-   [Patent Literature 1] Japanese Patent Application Laid-Open (JP-A)    No. 5-208911-   [Patent Literature 2] WO 92/20642-   [Patent Literature 3] EPA No. 92305703.8-   [Patent Literature 4] EPA No. 0566266-   [Patent Literature 5] EPA No. 0602851-   [Patent Literature 6] EPA No. 0520722-   [Patent Literature 7] WO 98/02434-   [Patent Literature 8] WO 02/066445-   [Patent Literature 9] WO 2004/0691545-   [Patent Literature 10] WO 2004/105765-   [Non-Patent Literature 1] Cancer Res., 1991, vol. 51, p. 4430-4435-   [Non-Patent Literature 2] Cancer Res., 1992, vol. 52, p. 3636-3641-   [Non-Patent Literature 3] Cancer Chemother. Pharmacol., 1993, vol.    32, p. 1-19-   [Non-Patent Literature 4] Expart. Opin. Invest. Drugs, 1994, vol. 3,    No. 6, p. 577-595-   [Non-Patent Literature 5] Cell, 1989, vol. 58, p. 287-292-   [Non-Patent Literature 6] Clin. Cancer Res., 1999, vol. 5, p.    4164-4174

DISCLOSURE OF INVENTION Problems to be Solved by the Invention

In comparison with a EGFR or HER2 selective inhibitor, a dual inhibitorfor both EGFR and HER2 is expected to be more efficacious, becauselatter inhibitor would show stronger effect in wider range of disease bysynergistic effect of dual inhibition. Therefore, a compound whichinhibits both of EGFR and HER2 has been desired.

Means to Solve the Problems

In the above situation, the present inventors intensively studied and,as a result, found out that a quinazoline derivative having a certainsubstituent at a 6-position has the excellent dual inhibitory activityon an EGF receptor and HER2.

That is, the present invention relates to:

(1) A compound represented by the general formula (I):

wherein R^(X) is a group represented by the formula:

wherein R¹ is a hydrogen atom, optionally substituted alkyl, optionallysubstituted alkenyl, optionally substituted aryl, or an optionallysubstituted non-aromatic nitrogen-containing heterocyclic group;Z is —O—, —N(R¹⁰)—, or alkylene which may be intervened with —O— or—N(R¹¹)—; whereinR¹⁰ and R¹¹ are independently a hydrogen atom, alkyl, acyl,alkyloxycarbonyl, alkenyloxycarbonyl, or aralkyloxycarbonyl;R² is a hydrogen atom, optionally substituted alkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted cycloalkyl, optionally substituted aryl, or optionallysubstituted heteroaryl;R¹⁹ is optionally substituted alkyl, optionally substituted aryl,optionally substituted heteroaryl, or an optionally substitutednon-aromatic heterocyclic group;R¹⁸ is a hydrogen atom, optionally substituted alkyl, optionallysubstituted alkenyl, or optionally substituted alkynyl;W¹ is an optionally substituted non-aromatic nitrogen-containingheterocyclic group or optionally substituted heteroaryl;R¹⁷ is a hydrogen atom, optionally substituted alkyl, optionallysubstituted alkenyl, or an optionally substituted non-aromaticnitrogen-containing heterocyclic group;R³ and R⁴ are independently a hydrogen atom, optionally substitutedalkyl, optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted alkyloxy, optionally substituted alkenyloxy,halogen, hydroxy, mercapto, or optionally substituted amino;X is —O—, —S—, —N(R¹²)—, or alkylene which may be intervened with —O—,—S—, or —N(R¹³)—;wherein R¹² and R¹³ are independently a hydrogen atom, alkyl, acyl,alkyloxycarbonyl, alkenyloxycarbonyl, or aralkyloxycarbonyl; andA is a group represented by the formula:

wherein R⁵ is a hydrogen atom, halogen, optionally substituted alkyloxy,optionally substituted alkenyloxy, optionally substituted alkynyloxy, ora group represented by the formula: —Y—R⁸ wherein Y is —O—, —S—, —SO₂—,or alkylene which may be intervened with —O—, —S—, or —N(R⁹)—, R⁸ isoptionally substituted aryl or optionally substituted heteroaryl;R⁹ is a hydrogen atom, alkyl, acyl, alkyloxycarbonyl,alkenyloxycarbonyl, or aralkyloxycarbonyl;R⁶ and R⁷ are independently a hydrogen atom, optionally substitutedalkyl, optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted alkyloxy, optionally substituted alkenyloxy,optionally substituted alkynyloxy, halogen, hydroxy, mercapto, cyano, oroptionally substituted amino;R²⁰ is optionally substituted alkyl, optionally substituted alkenyl,optionally substituted alkynyl, or a group represented by the formula:

wherein R⁵, R⁶ and R⁷ are as defined above;Q is N or CH,its pharmaceutically acceptable salt, or a solvate thereof.

More particularly, the present invention relates to the following (2) to(20).

(2) The compound according to (1), wherein R^(X) is a group representedby the formula:

wherein R¹, R², R¹⁸, R¹⁹, Z, and W¹ are as defined in (1), itspharmaceutically acceptable salt, or a solvate thereof(3) The compound according to (1) or (2), wherein R¹ is alkyl optionallysubstituted with a substituent selected from substituent group Aconsisting of hydroxy, heteroaryl, carboxy, optionally substitutedamino, optionally substituted non-aromatic nitrogen-containingheterocyclic group, optionally substituted aminocarbonyl, and optionallysubstituted non-aromatic nitrogen-containing heterocyclic carbonyl, or anon-aromatic nitrogen-containing heterocyclic group optionallysubstituted with a substituent selected from substituent group Bconsisting of alkyloxycarbonyl, optionally substituted aminocarbonyl,oxo, amino, carboxy, cyano, cyanoalkyl, hydroxyalkyl,alkylcarbonylamino, alkylsulfonylamino, and aminocarbonylalkyl,its pharmaceutically acceptable salt, or a solvate thereof.(4) The compound according to any one of (1) to (3), wherein R¹ is alkylsubstituted with amino optionally substituted with a substituentselected from substituent group C consisting of alkyl, alkenyl, alkynyl,optionally substituted aryl, araklyl, alkyloxy, hydroxyalkyl,hydroxyalkyoxyalkyl, haloalkyl, aminoalkyl optionally substituted with 1or 2 alkyls, alkylsulfonyl, alklysulfonylalkyl, alkylcarbonyl optionallysubstituted with halogen or alkyloxy, alkyloxycarbonyl, optionallysubstituted cycloalkyl, carboxyalkyl, optionally substitutedaminocarbonylalkyl, optionally substituted aminocarbonyloxyalkyl,alkyloxyalkyl, alkylthioalkyl, alkylcarbonylaminoalkyl,alkylsulfonylaminoalkyl, alkylsulfonyl(alkyl)aminoalkyl,alkyloxycarbonylalkyl, alkylthio(hydroxy)alkyl, cycloalkylalkyl,cyanoalkyl, optionally substituted aminoalkylcarbonyl, option allysubstituted heteroaryl, heteroarylalkyl, hydroxyalkyloxyalkyl,optionally substituted non-aromatic heterocyclic group, and optionallysubstituted non-aromatic heterocyclic alkyl,alkyl substituted with a non-aromatic nitrogen-containing heterocyclicgroup optionally substituted with a substituent selected fromsubstituent group D consisting of halogen; aryl; hydroxy; oxo;optionally substituted aminocarbonyl; alkyloxycarbonyl; alkyl optionallysubstituted with a substituent selected from substituent group Hconsisting of optionally substituted aminocarbonyl, cyano, alkyloxy,alkylsulfonylamino, amino, carboxy, alkyloxycarbonyl, and hydroxy;alkylaminocarbonyll; carboxy; cyano; alkylsulfonyl; alkylcarbonyl;alkenylcarbonyl; alkylsulfonylalkylcarbonyl; alkyloxy, alkylcarbonyl;alkylcarbonylamino; aminocarbonyloxy; a non-aromatic nitrogen-containingheterocyclic group; and non-aromatic heterocyclic carbonyl, or anon-aromatic nitrogen-containing heterocyclic group optionallysubstituted with a substituent selected from substituent group B,its pharmaceutically acceptable salt, or a solvate thereof.(5) The compound according to any one of (1) to (4), wherein Z is —O—,its pharmaceutically acceptable salt, or a solvate thereof.(6) The compound according to (1) or (2), wherein R¹⁹ is alkyloptionally substituted with a substituent selected from substituentgroup A;aryl optionally substituted with a substituent selected from substituentgroup I consisting of alkyloxycarbonyl, optionally substitutedaminocarbonyl, cyano, cyanoalkyl, hydroxyalkyl, and aminocarbonylalkyl,orheteroaryl optionally substituted with substituent selected fromsubstituent group I;its pharmaceutically acceptable salt, or a solvate thereof.(7) The compound according to any one of (1), (2), and (6), wherein R¹⁹is alkyl substituted with amino optionally substituted with asubstituent selected from a substituent group C; oralkyl substituted with a non-aromatic nitrogen-containing heterocyclicgroup optionally substituted with a substituent selected fromsubstituent group D; its pharmaceutically acceptable salt, or a solvatethereof.(8) The compound according to (1) or (2), wherein W¹ is a grouprepresented by a non-aromatic nitrogen-containing heterocyclic groupoptionally substituted with a substituent selected from substituentgroup J consisting of alkyl, cyanoalkyl, hydroxyalkyl,aminocarbonylalkyl, alkyloxy, alkyloxycarbonyl, optionally substitutedaminocarbonyl, and cyano; ora group represented by heteroaryl optionally substituted with asubstituent selected from substituent group J;its pharmaceutically acceptable salt, or a solvate thereof.(9) The compound according to any one of (1) to (8), wherein R² is ahydrogen atom, C1-C6 alkyl optionally substituted with halogen, C2-C6alkenyl, C2-C6 alkynyl, halogen, or phenyl, its pharmaceuticallyacceptable salt, or a solvate thereof.(10) The compound according to any one of (1) to (9), wherein R² isC2-C4 alkynyl,its pharmaceutically acceptable salt, or a solvate thereof(11) The compound according to any one of (1) to (10), wherein one of R³and R⁴ is a hydrogen atom, and the other is a hydrogen atom, optionallysubstituted alkyloxy or optionally substituted alkenyloxy,its pharmaceutically acceptable salt, or a solvate thereof.(12) The compound according to any one of (1) to (11), wherein X is—NH—, its pharmaceutically acceptable salt, or a solvate thereof.(13) The compound according to any one of (1) to (12), wherein A is agroup represented by the formula:

wherein R⁵ is a hydrogen atom or halogen; R⁶ is halogen or alkynyl; andR⁷ is a hydrogen atom,its pharmaceutically acceptable salt, or a solvate thereof.(14) The compound according to any one of (1) to (12), wherein A is agroup represented by the formula:

wherein R⁵ is alkyloxy optionally substituted with a substituentselected from substituent group E consisting of carboxy,alkoxyooxycarbonyl, cycloalkyl, and optionally substitutedaminocarbonyl;alkenyloxy optionally substituted with a substituent selected fromsubstituent group E; oralkynyloxy optionally substituted with a substituent selected fromsubstituent group E;R⁶ is optionally substituted alkynyl, optionally substituted alkyloxy,or halogen; andR⁷ is a hydrogen atom,its pharmaceutically acceptable salt, or a solvate thereof.(15) The compound according to any one of (1) to (12), wherein A is agroup represented by the formula:

wherein R⁵ is a group represented by the formula: —Y—R⁸ wherein Y isalkylene which may be intervened with —O—;R⁸ is phenyl optionally substituted with substituent selected from asubstituent group F consisting of halogen, carboxy, alkyl, haloalkyl,hydroxyalkyl, alkyloxy, alkyloxycarbonyl, and optionally substitutedamino; pyridyl optionally substituted with a substituent selected fromsubstituent group F;furyl optionally substituted with a substituent selected fromsubstituent group F;thienyl optionally substituted with a substituent selected fromsubstituent group F;thiazolyl optionally substituted with a substituent selected fromsubstituent group F; oroxazolyl optionally substituted with a substituent selected fromsubstituent group F;R⁶ is optionally substituted alkynyl, optionally substituted alkyloxy,or halogen; andR⁷ is a hydrogen atom.its pharmaceutically acceptable salt, or a solvate thereof.(16) The compound according to (1), wherein R^(X) is a group representedby the formula:

wherein R¹ is alkyl substituted with amino optionally substituted withalkyl, hydroxyalkyl, alkylcarbonylaminoalkyl or a non-aromaticheterocycle; alkyl substituted with a non-aromatic nitrogen-containingheterocycle optionally substituted with alkyl, hydroxyalkyl oralkylcarbonylamino; or a non-aromatic nitrogen-containing heterocyclicgroup substituted with hydroxyalkyl; and R² is C2-C4 alkynyl;R³ and R⁴ are both a hydrogen atom;X is —NH— andA is a group represented by the formula:

wherein R⁵ is a group represented by the formula: —Y—R, wherein Y isC1-C3 alkylene which may be intervened with —O—;R⁸ is phenyl optionally substituted with halogen, or pyridyl optionallysubstituted with halogen;R⁶ is halogen; andR⁷ is a hydrogen atom,its pharmaceutically acceptable salt, or a solvate thereof.(17) A pharmaceutical composition containing the compound as defined inany one of (1) to (16) as an active ingredient.(18) A pharmaceutical composition useful for treating cancer containingthe compound as defined in any one of (1) to (16) as an activeingredient.(19) A method for preventing and/or treating a cancer, comprisingadministering the compound according to any one of (1) to (16), itspharmaceutically acceptable salt or a solvate thereof.(20) Use of the compound according to any one of (1) to (16), itspharmaceutically acceptable solvate or a salt for producing acomposition for preventing and/or treating a cancer.

In addition, the present invention includes the following Inventions asother aspect.

(I) A compound represented by the general formula (I):

wherein R^(X) is a group represented by the formula:

wherein R¹ is a hydrogen atom, optionally substituted alkyl, optionallysubstituted alkenyl, or an optionally substituted non-aromaticnitrogen-containing heterocyclic group;Z is —O— or —N(R¹⁰)—, or alkylene which may be intervened with —O— or—N(R¹¹)—;R¹⁰ and R¹¹ are independently a hydrogen atom, alkyl, acyl,alkyloxycarbonyl, alkenyloxycarbonyl, or aralkyloxycarbonyl;R² is a hydrogen atom, optionally substituted alkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted aryl, or optionally substituted heteroaryl;R¹⁹ is optionally substituted alkyl, optionally substituted aryl,optionally substituted heteroaryl, or an optionally substitutednon-aromatic heterocyclic group;R¹⁸ is a hydrogen atom, optionally substituted alkyl, optionallysubstituted alkenyl, or optionally substituted alkylnyl;W¹ is an optionally substituted non-aromatic nitrogen-containingheterocyclic group or optionally substituted heteroaryl;R¹⁷ is a hydrogen group, optionally substituted alkyl, optionallysubstituted alkenyl, or optionally substituted non-aromaticnitrogen-containing heterocyclic group;R³ and R⁴ are independently a hydrogen atom, optionally substitutedalkyl, optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted alkyloxy, optionally substituted alkenyloxyhalogen, hydroxy mercapto, or optionally substituted amino;X is —O—, S—, —N(R¹²)—, or alkylene which may be intervened with —O—,—S—, or —N(R¹³)—; wherein R¹² and R¹³ are independently a hydrogen atom,alkyl, acyl, alkyloxycarbonyl, alkenyloxycarbonyl, oraralkyloxycarbonyl; andA is a group represented by the formula:

wherein R⁵ is a hydrogen atom, halogen, optionally substituted alkyloxy,optionally substituted alkenyloxy, optionally substituted alkynyloxy, ora group represented by the formula: —Y—R⁸ wherein Y is —O—, —S—, oralkylene which may be intervened with —N(R⁹)—; R⁸ is optionallysubstituted aryl, or optionally substituted heteroaryl; R⁹ is a hydrogenatom, alkyl, acyl, alkyloxycarbonyl, alkenyloxycarbonyl, oraralkyloxycarbonyl;R⁶ and R⁷ are independently a hydrogen atom, optionally substitutedalkyl, optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted alkyloxy, optionally substituted alkenyloxy,optionally substituted alkynyloxy, halogen, hydroxy, mercapto, oroptionally substituted amino;R²⁰ is optionally substituted alkyl, optionally substituted alkenyl,optionally substituted alkynyl, or a group represented by the formula:

wherein R⁵, R⁶ and R⁷ are as defined above:Q is N or CH₂,its pharmaceutically acceptable salt, or a solvate thereof.

More particularly, the present invention relates to the following (II)to (XV).

(II) A compound according to (I), wherein R^(X) is a group representedby the formula:

wherein R¹, R², R¹⁸, R¹⁹, Z, and W¹ are as defined in (I),its pharmaceutically acceptable salt, or a solvate thereof.(III) The compound according to (I) or (II), wherein R¹ is alkyloptionally substituted with a substituent selected from substituentgroup A′ consisting of hydroxy, optionally substituted amino, optionallysubstituted non-aromatic nitrogen-containing heterocyclic group,optionally substituted aminocarbonyl, and optionally substitutednon-aromatic nitrogen-containing heterocyclic carbonyl, ora non-aromatic nitrogen-containing heterocyclic group optionallysubstituted with a substituent selected from substituent group B′consisting of alkyloxycarbonyl, optionally substituted aminocarbonyl,cyano, cyanoalkyl, hydroxyalkyl, and aminocarbonylalkyl,its pharmaceutically acceptable salt, or a solvate thereof.(IV) The compound according to any one of (I) to (III), wherein R¹ isalkyl optionally substituted with amino substituted with a substituentselected from substituent group C′ consisting of alkyl, alkynyl,alkylsulfonylalkyl, hydroxyalkyl, alkylcarbonyl optionally substitutedwith halogen, alkyloxycarbonyl, cycloalkyl, optionally substituted withaminocarbonylalkyl, optionally substituted aminocarbonyloxyalkyl,alkyloxyalkyl, cycloalkylalkyl, cyanoalkyl, and optionally substitutedaminoalkylcarbonyl, or alkyl substituted with a non-aromaticnitrogen-containing heterocyclic group optionally substituted with asubstituent selected from a substituent group D′ consisting of hydroxy;oxo; optionally substituted aminocarbonyl; alkyloxycarbonyl; alkyloptionally substituted with a substituent selected from substituentgroup H′ consisting of optionally substituted aminocarbonyl, cyano,alkyloxy, and hydroxy; alkylaminocarbonyl; cyano; alkylsulfonyl;alkylcarbonyl; alkenylcarbonyl; alkylsulfonylalkylcarbonyl;alkyloxyalkylcarbonyl; alkylcabonylamino; and non-aromatic heterocycliccarbonyl,its pharmaceutically acceptable salt, or a solvate thereof.(V) The compound according to (I) or (II), wherein R¹⁹ is alkyloptionally substituted with a substituent selected from substituentgroup A′, aryl optionally substituted with a substituent selected fromsubstituent group I′ consisting of alkyloxycarbonyl, optionallysubstituted aminocarbonyl, cyano, cyanoalkyl, hydroxyalkyl, andaminocarbonylalkyl, orheteroaryl substituted with a substituent selected from substituentgroup I′,its pharmaceutically acceptable salt, or a solvate thereof.(VI) The compound according to any one of (I), (II) and (V), wherein R¹⁹is alkyl substituted with amino optionally substituted with asubstituent selected from substituent group C′, oralkyl substituted with a non-aromatic nitrogen-containing heterocyclicgroup optionally substituted with a substituent selected fromsubstituent group D′,its pharmaceutically acceptable salt, or a solvate thereof.(VII) The compound according to (I) or (II), wherein W¹ is a grouprepresented by a non-aromatic nitrogen-containing heterocyclic groupoptionally substituted with a substituent selected from substituentgroup J′ consisting of alkyl, cyanoalkyl, hydroxyalkyl,aminocarbonylalkyl, alkyloxy, alkyloxycarbonyl, optionally substitutedaminocarbonyl, and cyano, or a group represented by heteroaryloptionally substituted with a substituent selected from substituentgroup J′,its pharmaceutically acceptable salt, or a solvate thereof.(VIII) The compound according to any one of (1) to (VII), wherein R² isa hydrogen atom, C1-C6 alkyl optionally substituted halogen, C2-C6alkenyl, C2-C6 alkynyl, halogen, or phenyl,its pharmaceutically acceptable salt, or a solvate thereof.(IX) The compound according to any one of (I) to (VIII), wherein one ofR³ and R⁴ is a hydrogen atom, and the other is a hydrogen atom,optionally substituted alkyloxy or optionally substituted alkenyloxy,its pharmaceutically acceptable salt, or a solvate thereof.(X) The compound according to any one of (I) to (IX), wherein X is —NH—,its pharmaceutically acceptable salt, or a solvate thereof.(XI) The compound according to any one of (I) to (IX), wherein A is agroup represented by the formula:

wherein R⁵ is a hydrogen atom or halogen; R⁶ is halogen or alkynyl; andR⁷ is a hydrogen,its pharmaceutically acceptable salt, or a solvate thereof.(XII) The compound according to any one of (I) to (IX), wherein A is agroup represented by the formula:

wherein R is alkyloxy optionally substituted with a substituent selectedfrom substituent group E′ consisting of carboxy, alkyloxycarbonyl,cycloalkyl, and optionally substituted aminocarbonyl,alkenyloxy optionally substituted with a substituent selected fromsubstituent group E′, oralkynyloxy optionally substituted with a substituent selected fromsubstituent group E′;R⁶ is optionally substituted alkynyl, optionally substituted alkyloxy,or halogen; andR⁷ is a hydrogen atom,its pharmaceutically acceptable salt, or a solvate thereof.(XIII) The compound according to any one of (I) to (IX), wherein A is agroup represented by the formula:

wherein R⁵ is a group represented by the formula: —Y—R⁸ wherein Y isalkylene which may be intervened with —O—;R⁸ is phenyl optionally substituted with a substituent selected fromsubstituent group F′ consisting of halogen, carboxy, alkyl, haloalkyl,hydroxyalkyl, alkyloxy, alkyloxycarbonyl, and optionally substitutedamino; pyridyl optionally substituted with a substituent selected fromsubstituent group F′;furyl optionally substituted with a substituent selected from asubstituent group F′;thienyl optionally substituted with a substituent selected from asubstituent group F′;thiazolyl optionally substituted with a substituent selected from asubstituent group F′; oroxazolyl optionally substituted with a substituent selected from asubstituent group F′;R⁶ is optionally substituted alkynyl, optionally substituted alkyloxy,or halogen; andR⁷ is a hydrogen atom,its pharmaceutically acceptable salt, or a solvate thereof.(XIV) A pharmaceutical composition containing the compound as defined inany one of (I) to (XIII) as an active ingredient.(XV) A pharmaceutical composition useful for treating cancer containingthe compound as defined in any one of (I) to (XIII) as an activeingredient.(XVI) A method for preventing and/or treating a cancer, comprisingadministering the compound as defined in any one of (I) to (XIII), itspharmaceutically acceptable salt, or a solvate thereof.(XVII) Use of the compound as defined in any one of (I) to (XIII), itspharmaceutically acceptable salt, or a solvate thereof for producing acomposition for preventing and/or a cancer.

A still other aspect of the present invention includes the followinginventions.

(i) A compound represented by the general formula (I′):

wherein R¹ is a hydrogen atom, optionally substituted alkyl, optionallysubstituted alkenyl, or optionally substituted non-aromaticnitrogen-containing heterocyclic group;Z is —O— or —N(R¹⁰)—, or alkylene which may be intervened with —O— or—N(R¹¹)—;R¹⁰ and R¹¹ are independently a hydrogen atom, alkyl, acyl,alkyloxycarbonyl, alkenyloxycarbonyl, or aralkyloxycarbonyl;R² is a hydrogen atom, optionally substituted alkyl, alkenyl, alkynyl,optionally substituted aryl, or optionally substituted heteroaryl, or agroup represented by —C(R²)═N—Z—R¹ is a group represented by theformula:

wherein R¹⁷ is a hydrogen atom, optionally substituted alkyl, optionallysubstituted alkenyl, or an optionally substituted non-aromaticnitrogen-containing heterocyclic group;R³ and R⁴ are independently a hydrogen atom, optionally substitutedalkyl, optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted alkyloxy, optionally substituted alkenyloxy,halogen, hydroxy, mercapto or optionally substituted amino;X is —O—, —S—, or —N(R¹²)—, or alkylene which may be intervened with—O—, —S—, or —N(R¹³)—; wherein R¹² and R¹³ are independently a hydrogenatom, alkyl, acyl, alkyloxycarbonyl, alkenyloxycarbonyl, oraralkyloxycarbonyl; andA is a group represented by the formula:

wherein R⁵ is a hydrogen atom, halogen, optionally substituted alkyloxy,optionally substituted alkenyloxy, optionally substituted alkynyloxy, ora group represented by the formula: —Y—R⁸ wherein Y is —O—, —S—, oralkylene which may be intervened with —N(R⁹)—; R⁸ is optionallysubstituted aryl, or optionally substituted heteroaryl; R⁹ is a hydrogenatom, alkyl, acyl, alkyloxycarbonyl, alkenyloxycarbonyl, oraralkyloxycarbonyl;R⁶ and R⁷ are independently a hydrogen atom, optionally substitutedalkyl, optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted alkyloxy, optionally substituted alkenyloxy,optionally substituted alkynyloxy, halogen, hydroxy, mercapto, oroptionally substituted amino, its pharmaceutically acceptable salt, or asolvate thereof.(ii) The compound according to (i), wherein R¹ is alkyl optionallysubstituted with a substituent selected from substituent group A″consisting of optionally substituted amino and optionally substitutednon-aromatic nitrogen-containing heterocyclic group, ora non-aromatic nitrogen-containing heterocyclic group optionallysubstituted with a substituent selected from substituent group B″consisting of alkyloxycarbonyl, optionally substituted aminocarbonyl,and cyano, its pharmaceutically acceptable salt, or a solvate thereof.(iii) The compound according to (i) or (ii), wherein R¹ is alkylsubstituted with amino optionally substituted with a substituentselected from substituent group C″ consisting of alkyl,alkylsulfonylalkyl, alkylcarbonyl optionally substituted with halogen,alkyloxycarbonyl, cycloalkyl, optionally substituted aminocarbonylalkyl,optionally substituted aminocarbonyloxyalkyl, alkyloxyalkyl, andoptionally substituted aminoalkylcarbonyl, or alkyl substituted with anon-aromatic nitrogen-containing heterocyclic group optionallysubstituted with a substituent selected from substituent group D″consisting of oxo, optionally substituted aminocarbonyl,alkyloxycarbonyl, alkyl optionally substituted with cyano or alkyloxy,cyano, alkylsulfonyl, alkylcarbonyl, alkenylcarbonyl, andalkylsulfonylalkylcarbonyl, its pharmaceutically acceptable salt, or asolvate thereof.(iv) The compound according to any one of (i) to (iii), wherein one ofR³ and R⁴ is a hydrogen atom, and the other is a hydrogen atom,optionally substituted alkyloxy or optionally substituted alkenyloxy,its pharmaceutically acceptable salt, or a solvate thereof.(v) The compound according to any one of (i) to (iv), wherein X is —NH—,its pharmaceutically acceptable salt, or a solvate thereof.(vi) The compound according to any one of (i) to (v), wherein A is agroup represented by the formula:

wherein R⁵ is a hydrogen atom or halogen; R⁶ is halogen or alkynyl; andR⁷ is a hydrogen atom,its pharmaceutically acceptable salt, or a solvate thereof.(vii) The compound according to any one of (i) to (vi), wherein A is agroup represented by the formula:

wherein R⁵ is alkyloxy optionally substituted with a substituentselected from substituent group E″ consisting of carboxy,alkyloxycarbonyl, and optionally substituted aminocarbonyl,alkenyloxy optionally substituted with a substituent selected from asubstituent group E″, oralkynyloxy optionally substituted with a substituent selected from asubstituent group E″;R⁶ is optionally substituted alkynyl, optionally substituted alkyloxy,or halogen; andR⁷ is a hydrogen atom,its pharmaceutically acceptable salt, or a solvate thereof.(viii) The compound according to any one of (i) to (vii), wherein A is agroup represented by the formula:

wherein R⁵ is a group represented by the formula: —Y—R⁸ wherein Y isalkylene which may be intervened with —O—;R⁸ is phenyl optionally substituted with a substituent selected fromsubstituent group F″ consisting of halogen, carboxy, alkyl, haloalkyl,hydroxyalkyl, alkyloxy, alkyloxycarbonyl, and optionally substitutedamino; pyridyl optionally substituted with a substituent selected from asubstituent group F″;furyl optionally substituted with a substituent selected from asubstituent group F″;thienyl optionally substituted with a substituent selected from asubstituent group F″;thiazolyl optionally substituted with a substituent selected from asubstituent group F″; oroxazolyl optionally substituted with a substituent selected from asubstituent group F″;R⁶ is optionally substituted alkynyl, optionally substituted alkyloxy,or halogen; andR′ is a hydrogen atom,its pharmaceutically acceptable salt, or a solvate thereof.(ix) A pharmaceutical composition containing the compound as defined inany one of (i) to (viii) as an active ingredient.(x) A pharmaceutical composition useful for treating cancer containingthe compound as defined in any one of (i) to (viii) as an activeingredient.(xi) A method for preventing and/or treating a cancer, comprisingadministering the compound as defined in any one of (i) to (viii), itspharmaceutically acceptable salt, or a solvate thereof.(xii) Use of the compound as defined in any one of (i) to (viii), itspharmaceutically acceptable salt, or a solvate thereof for producing acomposition for preventing and/or treating a cancer.

As used herein, the “halogen” means fluorine, chlorine, bromine, oriodine. Fluorine, chorine, and bromine are preferable.

As used herein, the “alkyl” which is used alone or in combination withother term includes a straight or branched monovalent hydrocarbon grouphaving 1 to 10 carbon atom(s). Examples include methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,isopentyl, neo-pentyl, n-hexyl, isohexyl, n-heptyl, n-octyl, n-nonanyl,and n-decanyl. Preferable examples include C1-C10 alkyl. Furtherpreferable examples include C1-C6 alkyl. Most preferable examplesinclude C1-C4 alkyl.

As used herein, the term “haloalkyl” which is used alone or incombination with other term includes the “alkyl” which is substitutedwith the “halogen” at 1 to 8 places, preferably 1 to 5 places. Examplesinclude trifluoromethyl, trichloromethyl, difluoroethyl, trifluoroethyl,dichloroethyl, and trichloroethyl. Preferable examples include C1-C6alkyl which is substituted with the “halogen” at 1 to 5 places.Particularly, C1-C3 alkyl substituted with the “halogen” at 1 to 3places is preferable. Most preferable examples include trifluoromethyl.

As used herein, the “alkylsulfonyl” includes methylsulfonyl,ethylsulfony, and propylsulfonyl. Preferable examples include C1-C6alkylsulfonyl. Particularly, C1-C3 alkylsulfonyl is preferable.

As used herein, examples of the “alkylsulfonylalkyl” includemethylsulfonylmethyl, methylsulformylethyl, methylsulfonylpropyl,methylsulfonylbutyl, and methylsulfonylpropyl. Preferable examplesinclude C1-C6 alkylsulfonyl C1-C6 alkyl. Particularly, C1-C8alkylsulfonyl C1-C4 alkyl is preferable.

As used herein, examples of the “alkyloxy” include methyloxy, ethyloxy,n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, sec-butyloxy,tert-butyloxy, n-pentyloxy, n-hexyloxy, n-heptyloxy, n octyloxy,n-nonanyloxy, and n-decanyloxy. Preferable examples include C1-C6alkyloxy. Particularly, C1-C8 alkyloxy is preferable.

As used herein, examples of the “alkyloxyalkyl” include methyloxymethyl,methyloxyethyl, methyloxypropyl, ethyoxymethyl, ethyloxyethyl, andethyloxypropyl. Preferable examples include C1-C6 alkyloxy C1-C6 alkyl.Particularly, C1-C3 alkyloxy C1-C4 alkyl is preferable.

As used herein, examples of the “alkyloxycarbonyl” includemethyloxycarbonyl, ethyloxycarbonyl, n-propyloxycarbonyl,isopropyloxycarbonyl, n-butyloxycarbonyl, t-butyloxycarbonyl, andn-pentyloxycarbonyl. Preferable examples include C1-C6 alkyloxycarbonyl.Particularly, C1-C3 alkyloxycarbonyl is preferable.

As used herein, examples of the “alkylcarbonyl” include methylcarbonyl,ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonylt-butylcarbonyl, and n-pentylcarbonyl. Preferable examples include C1-C6alkylcarbonyl. Particularly, C1-C3 alkylcarbonyl is preferable.

As used herein, examples of the “haloalkyloxy” includetrifluoromethyloxy, trichloromethyloxy, difluoroethyloxy,trifluoroethyloxy, dichloroethyloxy, and trichloroethyloxy. Preferableexamples include halo C1-C6 alkyloxy. Particularly, halo C1-C3 alkyloxyis preferable. Most preferable examples include trifluoromethyloxy.

As used herein, examples of the “aminocarbonylalkyl” includeaminocarbonylmethyl, aminocarbonylethyl, aminocarbonylpropyl, andaminocarbonylbutyl. Preferable examples include aminocarbonyl C1-C6alkyl. Particularly, aminocarbonyl C1-C3 alkyl is preferable.

As used herein, examples of the “aminocarbonylakyloxy” includeaminocarbonylmethyloxy, aminocarbonylethyloxy, aminocarbonylpropyloxy,and aminocarbonylbutyloxy. Preferable examples include aminocarbonylC1-C6 alkyloxy. Particularly, aminocarbonyl C1-C3 alkyloxy ispreferable.

As used herein, examples of the “hydroxyalkyl” include hydroxymethyl,hydroxyethyl, hydroxypropyl, and hydroxybutyl. Preferable examplesinclude hydroxy C1-C6 alkyl. Particularly, hydroxy C1-C3 alkyl ispreferable.

As used herein, examples of the “alkylthio” include methylthio,ethylthio, propylthio, and butylthio. Preferable examples include C1-C6alkylthio. Particularly, C1-C3 alkylthio is preferable.

As used herein, the “alkylene” which is used alone or in combinationwith other term includes a straight or branched divalent hydrocarbongroup having 1 to 4 carbon atom(s). Examples include methylene,ethylene, propylene, and butylene. Preferable examples include C1-C3alkylene. Particularly, C1-C2 alkylene is preferable.

The “alkylene which may be intervened with —O— or —N(R¹¹)—” in Zincludes —CH₂—O—, —O—CH₂—, CH₂—N(R¹¹)—, —N(R¹³)CH₂—, —(CH₂)₂—O—,—O—(CH₂)₂—, —(CH₂)₂—N(R¹¹)—, and —N(R¹¹)—(CH)₂—. Particularly, —O—CH₂—,—N(R¹¹)—CH₂—, —O—(CH₂)₂—, and —N(R¹¹)—(CH₂)₂— are preferable.

The “alkylene which may be intervened with —O—, —S—, or —N(R¹²)—” in Xincludes —CH₂—O—, —O—CH₂—, —CH₂—S—, —S—CH₂—, CH₂—N(R¹²)—, —N(R¹²)—CH₂—,—(CH₂)₂—O—, —O—(CH₂)₂—, —(CH₂)₂—S—, —S—(CH₂)₂—, —(CH₂)₂—N(R¹²)—, and—N(R¹²)—(CH₂)₂—.

The “alkylene which may be intervened with —O—, —S—, or —N(R⁹)—” in Yincludes —CH₂—O—, —O—CH₂—CH₂S—, —S—CH₂—, —CH₂—N(R⁹)—, —N(R⁹)—CH₂—,—(CH)₂—O—, —O(CH₂)₂—, —(CH₂)₂—S—, —S—(CH₂)₂—, —(CH₂)N(R⁹)—,N(R⁹)(CH₂)₂—, and —O—CH(CH₃)—.

As used herein, the “cycloalkyl” which is used alone or in combinationwith other term includes cycloalkyl having 3 to 8 carbon atom(s).Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, and cyclooctyl. Preferable examples include C5-C6cycloalkyl.

As used herein, the “alkenyl” includes a straight or branched monovalenthydrocarbon having 2 to 8 carbon atom(s) and having 1 or 2 or moredouble bond(s). The alkenyl may have a triple bond in a chain. Examplesinclude vinyl, allyl, 1-propenyl, 2-propenyl, and various butenylisomers. Preferable examples include C2-C6 alkenyl. Further preferableexamples include C2-C4 alkenyl.

As used herein, examples of the “alkenyloxy” include vinyloxy, allyloxy,1-propenyloxy, 2-propenyloxy, and various butenyloxys. Preferableexamples include C2-C6 alkenyloxy. Particularly, C2-C4 alkenyloxy ispreferable.

As used herein, examples of the “alkenyloxycarbonyl” includevinyloxycarbonyl, allyloxycarbonyl, 1-propenyloxycarbonyl,2-propenyloxycarbonyl, and various butenyloxycarbonyls. Preferableexamples include C2-C6 alkenyloxycarbonyl. Particularly, C2-C4alkenyloxycarbonyl is preferable.

As used herein, the “alkynyl” includes a straight or branched monovalenthydrocarbon group having 2 to 8 carbon atom(s) and having 1 or 2 or moretriple bond(s). Examples include ethylnyl, 1-propynyl, 2-propynyl,1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, and variouspentynyl isomers. Preferable examples include C2-C6 alkynyl. Furtherpreferable examples include C2-C4 alkynyl.

As used herein, examples of the “alkynyloxy” include ethynyloxy,propynyloxy, butynyloxy, and pentynyloxy. Preferable examples includeC2-C6 alkynyloxy. Particularly, C2-C4 alkynyloxy is preferable.

As used herein, the “aryl” which is used alone or in combination withother term includes a monocyclic or fused cyclic aromatic hydrocarbon.Examples include phenyl, 1-naphthyl, 2-naphthyl, and anthryl. Phenyl,1-naphthyl, and 2-naphthyl are preferable. Particularly, phenyl ispreferable.

As used herein, the “aralkyl” includes the “alkyl” substituted with oneor two or more of the “aryl”, and these can be substituted at allpossible positions. Examples include benzyl, phenylethyl (e.g.2-phenylethyl, etc.), phenylpropyl (e.g. 3-phenylpropyl, etc.),naphthylmethyl (e.g. 1-naphthylmethyl, 2-naphthylmethyl, etc.), andanthrylmethyl (e.g. 9-anthrylmethyl, etc.). Preferable examples includebenzyl, and phenylethyl.

As used herein, examples of the “aralkyloxy” include benzyloxy,phenylethyloxy (e.g. 2-phenylethyloxy, etc.), phenylpropyloxy (e.g.3-phenylpropyloxy, etc.), naphthylmethyloxy (e.g. 1-naphthylmethyl,2-naphthylmethyloxy, etc.), anthrylmethyloxy (e.g. 9-anthrylmethyloxy,etc.). Preferable examples include benzyloxy, and phenylethyloxy.

As used herein, examples of the “aralkyloxycarbonyl” includebenzyloxycarbonyl, phenylethyloxycarbonyl (e.g.2-phenylethyloxycarbonyl, etc.), phenylpropyloxycarbonyl (e.g.3-phenylpropyloxycarbonyl, etc.), naphthylmethyloxycarbonyl (e.g.1-naphthylmethyl, 2-naphthylmethyloxycarbonyl, etc.),anthrylmethyloxycarbonyl (e.g. 9-anthrylmethyloxycarbonyl, etc.).Preferable examples include benzyloxycarbonyl, andphenylethyloxycarbonyl.

As used herein, the term “non-aromatic heterocyclic group” which is usedalone or in combination with other term includes a non-aromatic 5- to7-membered ring containing one or more arbitrary selected an oxygenatom, a sulfur atom or a nitrogen atom in a ring, and a group derivedfrom a ring in which other one or more “non-aromatic heterocyclicgroups” or “heteroaryls” is fused thereto. Examples include pyrrolidinyl(e.g. 1-pyrrolidinyl, 2-pyrrolidinyl), pyrrolinyl (e.g. 3-pyrrolinyl),imidazolidinyl (e.g. 2-imidazolidinyl), imidazolinyl (e.g.imidazolinyl), pyrazolidinyl (e.g. 1-pyrazolidinyl, 2-pyrazolidinyl),pyrazolinyl (e.g. pyrazolinyl), piperidyl (e.g. piperidino,2-piperidyl), piperazinyl (e.g. 1-piperazinyl, 2-piperazinyl), indolinyl(e.g. 1-indolinyl), isoindolinyl (e.g. isoindolinyl), morpholinyl (e.g.morpholino, 2-morphohnyl, 3-morpholinyl), tetrahydrofuranyl,dihydropyranyl, tetrahydropyranyl, dioxolanyl, tetrahydrothienyl,dihydrothiopyranyl, tetrahydrothiofuranyl, decahydroisoquinolinyl,azepinyl, oxepinyl, dihydrooxepinyl, tetrahydrooxepinyl, oxepanyl,4,5,6,7-tetrahydrothieno[3,2]pyridyl,2-oxa-5-aza-bicyclo[2.2.1]hepta-5-yl, andhexahydropyrazyl[2.1-b][1,3]ozadin-8-yl.

As the “non-aromatic heterocyclic group” in R¹⁹, pyrrodilinyl (e.g.1-pyrrodilinyl, 2-pyrrolidinyl), piperidyl (e.g. piperidino,2-piperidyl), piperazinyl (e.g. 1-piperazinyl), morpholinyl (e.g.morpholino, 3-morpholinyl), and tetrahydrofuranyl are preferable.

As used herein, a term “non-aromatic nitrogen-containing heterocyclicgroup” which is used alone, or in combination with other term includes anon-aromatic 4- to 7-membered ring containing at least one nitrogen atomin a ring and, further optionally, containing one or more atomsarbitrarily selected from an oxygen atom and a sulfur atom in a ring, ora group derived from a ring in which two or more of them are fused.Examples include azetidinyl (e.g. 1-azetidinyl, 2-azetidinyl,3-azetidinyl), pyrrolidinyl (e.g. 1-pyrrolidinyl, 2-pyrrolidinyl,3-pyrrolidinyl), pyrrolinyl (e.g. 3-pyrrolinyl), imidazolidinyl (e.g.2-imidazolidinyl), imidazolinyl (e.g. imidazolinyl), pyrazolidinyl (e.g.1-pyrazolidinyl, 2-pyrazolidinyl), pyrazolinyl (e.g. pyrazolinyl),piperidyl (e.g. piperidino, 2-piperidyl, 3-piperidyl, 4-piperidyl),piperazinyl (e.g. 1-piperazinyl, 2-piperazinyl), indolinyl (e.g.1-indolinyl), isoindolinyl (e.g. isoindolinyl), morpholinyl (e.g.morpholino, 2-morpholinyl, 3-morpholinyl), 1,4-thiazinyl (e.g.1,4-thiazin-1-yl, 1,4-thiazin-2-yl), thiomorpholinyl (e.g.1-thiomorpholinyl, 2-thiomorpholinyl), decahydroisoquinolyl (e.g.2-decahydroisoquinolyl), azepinyl (e.g. 1-azepinyl), diazepinyl,4,5,6,7-tetrahydrothieno[3,2]pyridyl,2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl, andhexahydropyrazyl[2.1-b][1,3]oxazin-3-yl.

As the “non-aromatic nitrogen-containing heterocyclic group” in R¹ andR¹⁷, azetidinyl (e.g. 1-azetidinyl, 2-azetidinyl, 3-azetidinyl),pyrrolidinyl (e.g. 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl), andpiperidyl (e.g. piperidino, 2-piperidyl, 3-piperidyl, 4-piperidyl) arepreferable.

As the “non-aromatic nitrogen-containing heterocyclic group” in W¹,azetidinyl (e.g. 1-azetidinyl, 2-azetidinyl, 3-azetidinyl), pyrrolidinyl(e.g. 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl), piperidyl (e.g.piperidino, 2-piperidyl, 3-piperidyl, 4-piperidyl), piperazinyl (e.g.1-piperazinyl), and morpholinyl (e.g. morpholino, 3-morpholinyl) arepreferable.

As the “non-aromatic nitrogen-containing heterocyclic group” in thesubstituent group A, pyrrolidinyl (e.g. 1-pyrrolidinyl, 2-pyrrolidinyl,3-pyrrolidinyl), piperidyl (e.g. piperidino, 2-piperidyl, 3-piperidyl,4-piperidyl), piperazinyl (e.g. 1-piperazinyl, 2-piperazinyl),morpholinyl (e.g. morpholino, 2-morpholinyl, 3-morpholinyl),thiomorpholinyl (e.g. 1-thiomorpholinyl, 2-thiomorpholinyl),decahydroisoquinolyl (e.g. 2-decahydroisoquinolyl), azepinyl (e.g.1-azepinyl), diazepinyl, 4,5,6,7-tetrahydrothieno[3,2]pyridyl,2-oxa-5-aza-bicyclo [2.2.1]hept-5-yl, andhexahydropyrazyl[2.1-b][1,3]oxazin-8-yl are preferable.

As used herein, the “heteroaryl” which is used alone, or in combinationwith other term includes a 5- to 6-membered aromatic group containingone or more of arbitrarily selected an oxygen atom, a sulfur atom and anitrogen atom in a ring. This may be fused with the “cycloalkyl”, the“aryl”, the “non-aromatic heterocyclic group”, or other heteroaryl atall possible positions. When heteroaryl is any of a monocycle and afused cycle, it can bind at all possible positions. Examples includepyrrolyl (e.g. 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl), furyl (e.g. 2-furyl,3-furyl), thienyl (e.g. 2-thienyl, 3-thienyl), imidazolyl (e.g.2-imidazolyl, 4-imidazolyl), pyrazolyl (e.g. 1-pyrazolyl, 3-pyrazolyl),isothiazolyl (e.g. 3-isothiazolyl), isooxazolyl (e.g. 3-isooxazolyl),oxazolyl (e.g. 2-oxazolyl), thiazolyl (e.g. 2-thiazolyl, 5-thiazolyl),pyridyl (e.g. 2-pyridyl, 3-pyridyl, 4-pyridyl), pyrazinyl (e.g.2-pyrazinyl), pyrimidinyl (e.g. 2-pyrimidinyl, 4-pyrimidinyl),pyridazinyl (e.g. 3-pyridazinyl), triazolyl, tetrazolyl (e.g.1H-tetrazolyl), oxadiazolyl (e.g. 1,3,4-oxadiazolyl), thiadiazolyl (e.g.1,3,4-thiadiazolyl), indolydinyl (e.g. 2-indolydinyl, 6-indolydinyl),isoindolyl (e.g. 2-isoindolyl), indolyl (e.g. 1-indolyl, 2-indolyl,3-indolyl), indazolyl (e.g. 3-indazolyl), purinyl (e.g. 8-purinyl),quinolizinyl (e.g. 2-quinolizinyl), isoquinolyl (e.g. 3-isoquinolyl),quinolyl (e.g. 2-quinolyl, 5-quinolyl), phthalazinyl (e.g.1-phthalazinyl), naphthyridinyl (e.g. 2-naphthyridinyl), quinolanyl(e.g. 2-quinolanyl), quinazolinyl (e.g. 2-quinazolinyl), cinnolinyl(e.g. 3-cinnolinyl), pteridinyl (e.g. 2-pteridinyl), carbazolyl (e.g.2-carbazolyl, 4-carbazolyl), phenanthridinyl (e.g. 2-phenanthridinyl,3-phenanthridinyl), acridinyl (e.g. 1-acridinyl, 2-acridinyl),dibenzofuranyl (e.g. 1-dibenzofuranyl, 2-dibenzofuranyl),benzoimidazolyl (e.g. 2-benzoimidazolyl), benzoisooxazolyl (e.g.3-benzoisooxazolyl), benzooxazolyl (e.g. 2-benzooxazolyl),bezooxadiazolyl (e.g. 4-benzooxadiazolyl), benzoisothiazolyl (e.g.3-benzoisothiazolyl), benzothiazolyl (e.g. 2-benzothiazolyl), benzofuryl(e.g. 3-benzofuryl), benzothienyl (e.g. 2-benzothienyl),4,5-dihydronaphtho[1,2-d]thiazolyl, 4H-chromeno[4,3-d]thiazolyl,4H-thiochromeno[4,3-d]thiazolyl, 4,5-dihydrothiazolo[5,4-c]quinolyl,8H-indeno[1,2-d]thiazolyl, and5,6-dihydro-4H-3-thia-1-aza-benzo[e]azuenyl.

As the “heteroaryl” in R², pyridyl, furyl, thienyl, thiazolyl, oxazolyl,thiadiazolyl, oxadiazolyl, and triazolyl are preferable. Furtherpreferable examples include pyridyl, furyl, thienyl, thiazolyl.

As the “heteroaryl” in R⁸, pyridyl, furyl, thienyl, thiazolyl, oxazolyl,thiadiazolyl, oxadiazolyl, and triazolyl are preferable. Furtherpreferable examples include pyridyl, furyl, thienyl, and thiazolyl.

As the “heteroaryl” in R¹⁹, pyridyl, furyl, and thienyl are preferable.

As the “heteroaryl” in W¹, pyrrolyl, imidazolyl, pyrazolyl, triazolyl,and tetrazolyl are preferable.

As used herein, the “heteroarylalkyl” includes the “alkyl” in which oneor two or more of the “heteroaryl” are replaced at an arbitrary positionthereof, and these can be substituted at all possible positions.Examples include thienylmethyl (e.g. 2-thienylmethyl), thienylethyl(e.g. 2-(thiophen-2-yl)ethyl), furylmethyl (e.g. 2-furylmethyl),furylethyl (e.g. 2-(furan-2-yl)ethyl), pyrrolylmethyl (e.g.2-pyrrolylmethyl), pyrrolylethyl (e.g. 2-(pyrrol-2-yl)ethyl),imidazolylmethyl (e.g. 2-imidazolylmethyl, 4-imidazolylmethyl),imidazolylethyl (e.g. 2-(imidazol-2-yl)ethyl), pyrazolylmethyl (e.g.3-pyrazolylmethyl), pyrazolylethyl (e.g. 2-(pyrazol-3-yl)ethyl),thiazolylmethyl (e.g. 2-thiazolylmethyl), thiazolylethyl (e.g.2-(thiazol-2-yl)ethyl), isothiazolylmethyl (e.g. 3-iso thiazolylmethyl),isooxazolylmethyl (e.g. 3-isooxazolylmethyl), oxazolylmethyl (e.g.2-oxazolylmethyl), oxazolylethyl (e.g. 2-(oxazol-2-yl)ethyl),pyridylmethyl (e.g. 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridiylmethyl),and pyridylethyl (e.g. 2-pyridylethyl).

As used herein, a term of the “acyl” which is used alone, or incombination with other term includes alkylcarbonyl in which an alkylpart is the “alkyl”, haloalkylcarbonyl in which a haloalkyl part is the“haloalkyl”, alkenylcarbonyl in which an alkenyl part is the “alkenyl”,aralkylcarbonyl in which an aralkyl part is the “aralkyl”, andarylcarbonyl in which an aryl part is the “aryl”. Examples includeacetyl, propionyl, butyroyl, trifluoromethylcarbonyl, vinylcarbonyl,phenylacetyl, and benzoyl. The “alkyl”, the “alkenyl” and the “aryl” maybe substituted with each substituent described below.

As the “acyl” in R¹⁰ and R¹¹, acetyl, benzoyl, and phenylacetyl arepreferable.

As the “acyl” in R¹² and R¹³, acetyl, benzoyl, and phenylacetyl arepreferable.

As the “acyl” in R⁹, acetyl, benzoyl, and phenylacetyl are preferable.

As used herein, examples of the “acyloxy” include acetyloxy,propionyloxy, and benzoyloxy.

As used herein, a term of the “optionally substituted amino” which isused alone, or in combination with other term includes amino optionallysubstituted with the “alkyl” optionally substituted with a substituentselected from substituent group A, the “haloalkyl”, the “alkenyl”, the“alkynyl”, the “alkylsulfonyl”, the “alkylsulfonylalkyl”, the“alkyloxycarbonyl”, the “aminocarbonyloxyalkyl”, the “alkyloxy”, the“alkyloxyalkyl” optionally substituted with a substituent selected fromsubstituent group A, the “cycloalkyl” optionally substituted with asubstituent selected from substituent group A, the “aryl” optionallysubstituted with a substituent selected from substituent group Gconsisting of alkyl, alkenyl, and aralkyl, the “aralkyl”, the“heteroaryl”, the “heteroarylalkyl”, the “acyl”, the“aminocarbonylalkyl” optionally substituted with a substituent selectedfrom substituent group G, the “aminoalkylcarbonyl” optionallysubstituted with a substituent selected from substituent group G,“alkenyloxycarbonyl” in which an alkenyloxy part is the “alkenyloxy”,and “aralkyloxycarbonyl” in which an aralkyloxy part is the “aralkyloxy”at one or two place(s). Examples include amino, methylamino,dimethylamino, ethylmethylamino, diethylamino, ethylmethylamino,diisopropylamino, benzylamino, acetylamino, trifluoromethylcarbonyl,benzoylamino, methyloxycarbonylamino, ethyloxycarbonylamino,n-propyloxycarbonylamino, isopropyloxycarbonylamino, n-butyloxy,isobutyloxycarbonylamino, sec-butyloxycarbonylamino,tert-butyloxycarbonylamino, alyloxycarbonylamino,benzyloxycarbonylamino, cyclopentylamino, and cyclohexylamino.

As a substituent of the “optionally substituted amino” in R³ and R⁴,alkyl, acyl, and the like are preferable.

As a substituent of the “optionally substituted amino” in R⁶ and R⁷,alkyl and the like are preferable.

As a substituent of the “optionally substituted amino” and the“optionally substituted aminocarbonyl” in substituent group A, alkyl,alkenyl, alkynyl, aryl optionally substituted with a substituentselected from substituent group I, aralkyl, alkyloxy, hydroxyalkyl,hydroxyalkyloxyalkyl, haloalkyl, aminoalkyl optionally substituted with1 or 2 alkyl(s), alkylsulfonyl, alkylsulfonylalkyl, alkylcarbonyloptionally substituted with halogen or alkyloxy, alkyloxycarbonyl,cycloalkyl optionally substituted with a substituent selected fromsubstituent group I, carboxyalkyl, aminocarbonylalkyl optionallysubstituted with a substituent selected from substituent group G,aminocarbonyloxyalkyl optionally substituted with a substituent selectedfrom substituent group G, alkyloxyalkyl, alkylthioalkyl,alkylcarbonylaminoalkyl, alkylsulfonylaminoalkyl,alkylsulfonyl(alkyl)aminoalkyl, alkyloxycarbonylalkyl,alkylthio(hydroxy) alkyl, cycloalkylalkyl, cyanoalkyl,aminoalkylcarbonyl optionally substituted with a substituent selectedfrom substituent group G, heteroaryl optionally substituted with asubstituent selected from substituent group C, heteroarylalkyl,hydroxyalkyloxyalkyl, a non-aromatic heterocyclic group optionallysubstituted with a substituent selected from substituent group 1, and anon-aromatic heterocyclic alkyl optionally substituted with asubstituent selected from substituent group I.

Herein, as a substituent in the “optionally substituted aminocarbonyl”,alkyl, alkenyl, aralkyl, and the like are preferable. Particularly,alkyl is preferable.

As a substituent in the “optionally substituted aminocarbonyl” in asubstituent group B, alkyl, alkenyl, aralkyl, and the like arepreferable.

As a substituent in the “optionally substituted aminocarbonyl” in asubstituent group D, alkyl, alkenyl, aralkyl, and the like arepreferable.

As a substituent in the “optionally substituted aminocarbonyl” in asubstituent group E, alkyl, alkenyl, aralkyl, and the like arepreferable.

As a substituent in the “optionally substituted aminocarbonyl” in asubstituent group H, alkyl, alkenyl, aralkyl, and the like arepreferable.

Herein, as a substituent in the “optionally substitutedaminocarbonylalkyl”, alkyl, alkenyl aralkyl, and the like arepreferable. Particularly, alkyl is preferable.

As a substituent in the “optionally substituted aminocarbonylalkyl” in asubstituent group C, alkylalkenyl, aralkyl, and the like are preferable.

Herein, as a substituent in the “optionally substitutedaminocarbonyloxyalkyl”, alkyl, alkenyl, aralkyl, and the like arepreferable. Particularly, alkyl is preferable.

As a substituent in the “optionally substituted aminocarbonyloxyalkyl”in a substituent group C, alkyl, alkenyl, aralkyl, and the like arepreferable.

Herein, as a substituent in the “optionally substitutedaminoalkylcarbonyl”, alkyl, alkenyl, aralkyl, and the like arepreferable. Particularly, alkyl is preferable.

As a substituent in the “optionally substituted aminoalkylcarbonyl” in asubstituent group C, alkyl, alkenyl, aralkyl, and the like arepreferable.

Herein, a term of the “optionally substituted ureido” includes ureidooptionally substituted with the “alkyl”, the “cycloalkyl”, the “aryl”,the “aralkyl”, the “heteroaryl”, the “heteroarylalkyl”, the “acyl”,cyanoalkyl, or alkyloxyalkyl at one or two or more places.

Herein, a term of the “optionally substituted guanidino” includesguanidino optionally substituted with the “alkyl”, the “cycloalkyl”, the“aryl”, the “aralkyl”, the “heteroaryl”, the “heteroarylalkyl”, the“acyl”, cyano, cyanoalkyl or alkyloxyalkyl at one or two or more places.

Herein, examples of a substituent in the “optionally substituted alkyl”include optionally substituted amino, an optionally substitutednon-aromatic nitrogen-containing heterocyclic group, optionallysubstituted non-aromatic nitrogen-containing heterocyclic carbonyl,alkyl, alkyloxy, cyano, alkylsulfonyl, cylcoalkyl, alkenyl, heteroaryl,heteroaryloxy, hydroxy, mercapto, alkylthio, halogen, nitro, carboxy,alkyloxycarbonyl, hydroxyalkyl, haloalkyl, haloalkyloxy,alkylcarbonyloxy, carbamoyloxy, optionally substituted aminocarbonyl,aminocarbonylalkyloxy, acyl, acyloxy, aryloxy, aralkyl, aralkyloxy,optionally substituted guanidino, an azo group, and optionallysubstituted ureido. These can be substituted with one or moresubstituent(s) at all possible positions.

As a substituent in the “optionally substituted alkyl” in R¹, R¹⁷ andR¹⁹, a substituent selected from substituent group A, alkyloxy, cyano,halogen, heteroaryl, and the like are preferable. Particularly, aminooptionally substituted with a substituent selected from substituentgroup C, and a non-aromatic nitrogen-containing heterocyclic groupoptionally substituted with a substituent selected from substituentgroup D are preferable.

As a substituent of the “optionally substituted alkyl” in R², asubstituent selected from substituent group A, alkyloxy, alkylcarbonyl,and halogen are preferable. Particularly, hydroxy, alkyloxy, and halogenare preferable.

As a substituent of the “optionally substituted alkyl” in R³ and R⁴,alkyloxy, alkyloxycarbonyl, aminocarbonyl, cyano, and the like arepreferable.

As a substituent of the “optionally substituted alkyl” in R⁶ and R⁷,alkyloxy, alkyloxycarbonyl, aminocarbonyl, cyano, hydroxy, and the likeare preferable.

As a substituent of the “optionally substituted alkyl” in R¹⁸, hydroxy,alkyloxy, halogen, cyano, and the like are preferable.

As a substituent of the “optionally substituted alkyl” in R²⁰, hydroxy,alkyloxy, halogen, cyano, and the like are preferable.

Herein, examples of a substituent in the “optionally substitutedalkenyl” and the “optionally substituted alkynyl” include optionallysubstituted amino, an optionally substituted non-aromaticnitrogen-containing heterocyclic group, cycloalkyl, hydroxy, alkyloxy,mercapto, alkylthio, halogen, nitro, cyano, carboxy, alkyloxycarbonyl,haloalkyl, haloalkyloxy, optionally substituted aminocarbonyl, acyl,acyloxy, aryl, aryloxy, aralkyl, aralkyloxy, alkylsulfonyl, guanidino,an azo group, optionally substituted ureido, and the like. These can besubstituted with one or more substituent(s) at all possible positions.

As a substituent of the “optionally substituted alkenyl” in R¹ and R¹⁷,a substituent selected from substituent group A is preferable. Inparticular, amino optionally substituted with a substituent selectedfrom substituent group C, and a non-aromatic nitrogen-containingheterocyclic group optionally substituted with a substituent selectedfrom substituent group D are preferable.

As a substituent of the “optionally substituted alkenyl” and the“optionally substituted alkynyl” in R², a substituent selected fromsubstituent group A, cycloalkyl, alkyloxy, and halogen are preferable.Particularly, hydroxy, cycloalkyl, alkyloxy, and halogen are preferable.

As a substituent of the “optionally substituted alkenyl” and the“optionally substituted alkynyl” in R³ and R⁴, alkyloxy,alkyloxycarbonyl, aminocarbonyl, alkyl optionally substituted with cyanoand the like, alkyloxy, alkyloxycarbonyl, aminocarbonyl,alkyloxycarbonyl optionally substituted with cyano and the like, andoptionally substituted aminocarbonyl, and the like are preferable.

As a substituent of the “optionally substituted alkenyl” and the“optionally substituted alkynyl” in R⁶ and R⁷, alkyloxy,alkyloxycarbonyl, aminocarbonyl, alkyl optionally substituted with cyanoand the like, alkyloxy, alkyloxycarbonyl, aminocarbonyl, alkylcarbonyl,aminocarbonyl, alkyloxycarbonyl optionally substituted with cyano andthe like, and optionally substituted aminocarbonyl, and the like arepreferable.

As a substituent of the “optionally substituted alkenyl” and the“optionally substituted alkynyl” in R¹⁸, hydroxy, alkyloxy, halogen,cyano, and the like are preferable.

As a substituent of the “optionally substituted alkenyl” and the“optionally substituted alkynyl” in R²⁰, hydroxy, alkyloxy, halogen,cyano, and the like are preferable.

Herein, examples of a substituent in the “optionally substitutedcycloalkyl” include alkyloxycarbonyl, aminocarbonyl optionallysubstituted with a substituent selected from substituent group G, cyano,alkyl optionally substituted with a substituent selected fromsubstituent group M consisting of cyano, hydroxy, carboxy,aminocarbonyl, alkyloxycarbonyl, and alkyloxy, alkylsulfonyl,alkylsulfonylalkylcarbonyl, cycloalkyl, hydroxy, alkyloxy, mercapto,alkylthio, halogen, nitro, carboxy, haloalkyl, haloalkyloxy, acyl,acyloxy, aryl, aryloxy (e.g. phenyloxy), aralkyl, aralkyloxy (e.g.benzyloxy), a non-aromatic nitrogen-containing heterocyclic group,alkylcarbonylamino, aminocarbonyloxy, amino, oxo, guanidino, an azogroup, and optionally substituted ureido.

As a substituent of the “optionally substituted cycloalkyl” insubstituent group C, substituents exemplified in substituent group I arepreferable.

Herein, examples of a substituent of the “optionally substitutedalkyloxy”, the “optionally substituted alkenyloxy”, and the “optionallysubstituted alkynyloxy” include cycloalkyl, alkenyl, hydroxy, alkyloxy,mercapto, alkylthio, halogen, nitro, cyano, carboxy, alkyloxycarbonyl,haloalkyl, haloalkyloxy, optionally substituted amino, optionallysubstituted aminocarbony, acyl, acyloxy, an optionally substitutednon-aromatic heterocyclic group, aryloxy, aralkyloxy, alkylsulfonyl,guanidino, an azo group, and optionally substituted ureido. These canreplace at one or more places of all possible positions. Preferableexamples include halogen.

As a substituent of the “optionally substituted alkyloxy” and the“optionally substituted alkenyloxy” in R³ and R⁴, alkyloxy, optionallysubstituted amino, a non-aromatic heterocyclic group optionallysubstituted with a substituent selected from substituent group D, cyano,and the like are preferable.

As a substituent of the “optionally substituted alkyloxy”, the“optionally substituted alkenyloxy”, and the “optionally substitutedalkynyloxy” in R⁵, a substituent selected from substituent group E ispreferable.

As a substituent of the “optionally substituted alkyloxy”, the“optionally substituted alkenyloxy”, and the “optionally substitutedalkynyloxy” in R⁶ and R⁷, alkyloxy, cyano, alkyloxycarbonyl, optionallysubstituted aminocarbonyl, and the like are preferable.

Herein, examples of a substituent in the “optionally substitutednon-aromatic heterocyclic group” include alkyloxycarbonyl, aminocarbonyloptionally substituted with a substituent selected from substituentgroup G, cyano, alkyl optionally substituted with a substituent selectedfrom substituent group M consisting of cyano, hydroxy, carboxy,aminocarbonyl, alkyloxycarbony, and alkyloxy, alkylsulfonyl,alkylsulfonylalkylcarbonyl, cycloalkyl, hydroxy, alkyloxy, mercapto,alkylthio, halogen, nitro, carboxy, haloalkyl, haloalkyloxy, acyl,acyloxy, aryl, aryloxy (e.g. phenyloxy), aralkyl, aralkyloxy (e.g.benzyloxy), a non-aromatic nitrogen-containing heterocyclic group,alkylcarbonylamino, aminocarbonyloxy, amino, Oxo, guanidino, an azogroup, and optionally substituted ureido.

Herein, examples of a substituent in the “optionally substitutednon-aromatic nitrogen containing heterocyclic group” includealkyloxycarbonyl, aminocarbonyl optionally substituted with asubstituent selected from substituent group G, cyano, alkyl optionallysubstituted with a substituent selected from substituent group Mconsisting of cyano, hydroxy, carboxy, aminocarbonyl, alkyloxycarbonyl,and alkyloxy, alkylsulfonyl, alkylsulfonylalkylcarbonyl, cycloalkyl,hydroxy, alkyloxy, mercapto, alkylthio, halogen, nitro, carboxy,haloalkyl, haloalkyloxy, acyl, acyloxy, aryl, aryloxy (e.g. phenyloxy),aralkyl, aralkyloxy (e.g. benzyloxy), a non-aromatic nitrogen-containingheterocyclic group, alkylcarbonylamino, aminocarbonyloxy, optionallysubstituted amino, oxo, guanidino, an azo group, and optionallysubstituted ureido.

As a substituent of the “optionally substituted non-aromaticnitrogen-containing heterocyclic group” in R¹ and R¹⁷, alkyl,alkyloxycarbonyl, aminocarbonyl optionally substituted with asubstituent selected from substituent group G, cyano, oxo, amino,carboxyl, hydroxyalkyl, cyanoalkyl, alkyloxyalkyl, alkylsulfonyl,alkylcarbonyl, alkenylcarbonyl, alkylsulfonylalkylcarbonyl,alkylcarbonylamino, alkylsulfonylamino, carboxyalkyl,alkyloxycarbonylalkyl, and the like are preferable. Particularly,substituents exemplified in substituent group B are preferable.

As a substituent of the “optionally substituted non-aromaticnitrogen-containing heterocyclic group” in W¹, alkyl, alkyloxycarbonyl,optionally substituted aminocarbonyl, cyano, hydroxyalkyl, cyanoalkyl,alkyloxyalkyl, alkylsulfonyl, alkylcarbonyl, alkenylcarbonyl,alkylsulfonylalkylcarbonyl, and the like are preferable. Particularly,substituents exemplified in substituent group J are preferable.

As a substituent of the “optionally substituted non-aromaticnitrogen-containing heterocyclic group” and the “optionally substitutednon-aromatic nitrogen-containing heterocyclic carbonyl” in substituentgroup A, a substituent selected from substituent group D is preferable.

Herein, examples of a substituent in the “optionally substituted aryl”,the “optionally substituted phenyl”, the “optionally substitutedheteroaryl”, the “optionally substituted pyridyl”, the “optionallysubstituted furyl”, the “optionally substituted thienyl”, the“optionally substituted thiazolyl”, the “optionally substitutedoxazolyl”, the “optionally substituted non-aromatic heterocyclic group”,the “optionally substituted non-aromatic heterocyclic alkyl”, the“optionally substituted cycloalkyl”, the “optionally substitutedaralkyl”, and the “optionally substituted heteroarylalkyl” includeoptionally substituted alkyl (as a substituent, halogen, hydroxy, nitro,cyano, carboxy, alkyloxy, alkyloxycarbonyl, acyl, etc), cycloalkyl,alkenyl, alkynyl, hydroxy, alkyloxy, aralkyloxy, mercapto, alkylthio,halogen, nitro, cyano, carboxy, alkyloxycarbonyl, aryloxycarbonyl,haloalkyl, haloalkyloxy, optionally substituted amino, optionallysubstituted aminocarbonyl, acyl, acyloxy, optionally substituted aryl(as a substituent, halogen, hydroxy, nitro, cyano, carboxy, alkyloxy,alkyloxycarbonyl, acyl, etc.), optionally substituted heteroaryl (as asubstituent, halogen, hydroxy, nitro, cyano, carboxy, alkyloxy,alkyloxycarbonyl, acyl, etc.), an optionally substituted non-aromaticheterocyclic group (as a substituent, halogen, hydroxy, nitro, cyano,carboxy, alkyloxy, alkyloxycarbonyl, acyl, etc.), optionally substitutedaralkyl (as a substituent, halogen, hydroxy, nitro, cyano, carboxy,alkyloxy, alkyloxycarbonyl, acyl, etc.), alkylsulfonyl, guanidino, anazo group, —N═N— (optionally substituted phenyl), and optionallysubstituted ureido. These can replace at one or more of all possibleposition(s).

As a substituent of the “optionally substituted aryl” in R¹,substituents exemplified in substituent group I are preferable.

As a substituent of the “optionally substituted aryl” and the“optionally substituted heteroaryl” in R², alkyl optionally substitutedwith hydroxy or optionally substituted amino, optionally substitutedamino, halogen, and the like are preferable. Particularly, alkyloptionally substituted with hydroxy or optionally substituted amino ispreferable.

As a substituent of the “optionally substituted aryl”, the “optionallysubstituted heteroaryl”, and the “optionally substituted non-aromaticheterocyclic group” in R⁸, alkyloxycarbonyl, optionally substitutedaminocarbonyl, cyano, halogen, alkyl, alkyloxy, alkylthio, haloalkyl,and the like are preferable. Particularly, substituents exemplified insubstituent group F are preferable.

As a substituent of the “optionally substituted aryl” and the“optionally substituted heteroaryl” in R¹⁹, alkyloxycarbonyl, optionallysubstituted aminocarbonyl, cyano, cyanoalkyl, hydroxyalkyl,aminocarbonylalkyl, and the like are preferable. Particularlysubstituents exemplified in substituent group I are preferable.

As a substituent of the “optionally substituted heteroaryl” in W¹,alkyl, hydroxy, alkyloxy, and the like are preferable. Particularly,substituents exemplified in substituent group J are preferable.

As a substituent of the “optionally substituted aryl”, the “optionallysubstituted heteroaryl”, the “optionally substituted non-aromaticheterocyclic group” and the “optionally substituted non-aromaticheterocyclic alkyl” in a substituent group C, substituents exemplifiedin substituent group I are preferable.

Herein, the “pharmaceutical composition useful for treating cancer” andthe “therapeutic for a cancer” include therapeutics for brain tumor(e.g. glioblastoma), urinary organ cancer (e.g. bladder cancer, kidneycancer), genital cancer (prostate cancer, ovary cancer, uterine cancer),lymphoid tumor, digestive tract cancer (e.g. stomach cancer, largeintestine cancer), pharynx cancer, lung cancer (e.g. lung gland cancer,small cell lung cancer, non-small cell lung cancer), pancreas cancer,breast cancer, head and neck cancer, esophagus cancer, and thyroidgland. Particularly, the composition is preferably used as therapeuticsfor breast cancer, brain tumor, bladder cancer, kidney cancer, prostatecancer, ovary cancer, uterine cancer, lung cancer, pancreas cancer,large intestine cancer, and head and neck cancer.

The present invention includes a method for treating or preventing acancer in a mammal in which it is necessary to treat or prevent acancer, and the method comprises administering a therapeuticallyeffective amount of the compound of the formula (I) to the mammal. Acancer which is preferably treated is selected from brain tumor (e.g.glioblastoma), urinary organ cancer (e.g. bladder cancer, kidneycancer), genital cancer (prostate cancer, ovary cancer, uterine cancer),lymphoid tumor, digestive tract cancer (e.g. stomach cancer), pharynxcancer, lung cancer, (e.g. lung gland cancer, small cell lung cancer,non-small cell lung cancer), pancreas cancer, breast cancer, head andneck cancer, esophagus cancer, and thyroid gland. More preferable arebreast cancer, brain tumor, bladder cancer, kidney cancer, prostatecancer, ovary cancer, uterine cancer, lung cancer, pancreas cancer,large intestine cancer, and head and neck cancer.

EFFECT OF THE INVENTION

The present compound has the excellent action of inhibiting an EGFreceptor and HER2, and has high safety (has reduced CYP inhibitoryactivity) and, therefore, it is useful as a medicament, inter alia, atherapeutic for a cancer.

Best Mode for Carrying out the Invention

The present compound (I) can be synthesized by any of methods A to Edescribed below. Alternatively, since a method of synthesizing aquinazoline derivative is described in WO 96/09294, WO 98/02434 and thelike, the present compound (I) can be also synthesized according tothis. When the compound has a group influencing on each reaction, thegroup can be protected with a suitable protecting group, and can bedeprotected at a suitable stage. In addition, when a raw material, areagent, an intermediate, and a reaction product at each step can form asalt, the salt is included.

wherein Hal¹ and Hal² are each independently halogen; R¹, R⁵, R⁶, and R⁷are as defined in (1).(Step 1)

The first step is a step of synthesizing a compound (iii) by reacting astarting raw material (S.M.) which can be synthesized according to themethod described in WO 96/09294 or the like, or is commerciallyavailable, and a compound (II) which can be synthesized according to themethod described in WO 98/02434 or the like, or is commerciallyavailable.

The starting raw material (S.M.) and the compound (ii) can be reacted ina solvent such as tetrahydrofuran, acetonitrile and the like at 20° C.to under heat refluxing, preferably at 60° C. to under heat refluxing,to obtain the compound (iii).

(Step 2)

The second step is a step of inserting carbon monoxide into the compound(iii) in the presence of a palladium catalyst to obtain a compound (iv).

The compound (iii) can be reacted at 50° C. to 150° C., preferably 70°C. to 90° C. under the carbon monoxide atmosphere in a solvent such asN,N-dimethylformamide, N,N-dimethylacetamide,N,N′-dimethylimidazolidinone, dimethyl sulfoxide and the like, in thepresence of a hydrogen source such as sodium formate, tributyltinhydride and the like, a palladium catalyst such asdichlorobis(triphenylphosphine)palladium,tetrakis(triphenylphosphine)palladium,tris(dibenzylideneacetone)dipalladium.[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium, palladiumacetate+triphenylphosphine and the like, and a base such astriethylamine, di(isopropyl)ethylamine and the like to obtain thecompound (iv).

(Step 3)

The third step is a step of synthesizing an objective compound (v) byreacting the compound (iv) and a compound represented by the formula:R¹—O—NH₂ wherein R¹ is as defined in (1).

The starting raw material (iv) and the compound represented by theformula: R¹—O—NH₂ wherein R¹ is as defined in (1) or a salt can bereacted at 0° C. to under heat refluxing, preferably at 20° C. to 70° C.in a solvent such as tetrahydrofuran, dioxane, methanol and the like, orin a mixed solvent of them and water, if necessary, in the presence ofan acid such as hydrochloric acid, sulfuric acid, p-toluenesulfonicacid, methanesulfonic acid, formic acid, acetic acid, trifluoroaceticacid and the like to obtain the compound (v).

wherein R¹, R⁵, R⁶, and R⁷ are as defined in (1).(Step 1)

The first step is a step of synthesizing an objective compound (v) byreacting a compound (v′) obtained by reacting the compound (iv) obtainedin the Method A with hydroxylamine, and a compound represented by theformula: R¹-Hal³ wherein Hal³ is halogen; R¹ is as defined in (1).

The compound (v′) and the compound represented by the formula: R¹-Hal³wherein Hal³ is halogen; R¹ is as defined in (1) can be dissolved in asolvent such as N,N-dimethylacetamide, N,N-dimethylacetamide,N,N′-dimethylmidazolidinone, dimethyl sulfoxide and the like, andreacted at 50° C. to 150° C., preferably 60° C. to 80° C. in thepresence of a base such as potassium carbonate, sodium carbonate, andthe like to obtain the compound (v).

Wherein R¹, R⁵, R⁶, and R⁷ as defined in (1).(Step 1)

The first step is a step of synthesizing an objective compound (xv) byreacting a compound (v′) obtained by reacting the compound (iv) obtainedin the Method A with hydroxylamine, and a compound represented by theformula: R¹—CH═CH₂ wherein R¹ is as defined in (1).

The compound (xv) can be obtained by dissolving the compound (v′) in asolvent such as chloroform, dichloromethane, 1,2-dichloroethane and thelike, and reacting with a chlorine-based oxidizing agent such asN-chlorosuccinimide, N-chlorophthalimide and the like at 20° C. to 100°C., preferably 50° C. to 60° C. in the presence of a catalytic amount ofa based such as pyridine, 4-dimethylaminopyridine and the like,subsequently, adding a compound represented by the formula: R¹—CH═CH₂wherein R¹ is as defined in (1), and a base such as triethylamine,di(isopropyl)ethylamine and the like, and reacting them at 0° C. to 100°C., preferably 10° C. to 30° C.

Wherein R¹, R², R⁵, R⁶, and R⁷ are as defined in (1)(Step 1)

the first step is a step of reacting the compound (iv) obtained inMethod A with a reagent represented by the formula: R²MgHal⁴ or R²Liwherein Hal⁴ is halogen; R² is as defined in (1) to obtain a compound(vi).

The compound (vi) can be obtained by reacting the compound (iv) and thereagent represented by the formula: R²MgHal⁴ or R²Li wherein Hal⁴ ishalogen; R² is as defined in (1) at −100° C. to 50° C., preferably −78°C. to 10° C. in a solvent such as tetrahydrofuran, diethyl ether,toluene, n-hexane and the like.

(Step 2)

The second step is a step of oxidizing the compound (vi) to synthesize acompound (vii).

The compound (vii) can be obtained by oxidizing the compound (vi) by ageneral method of oxidizing a secondary alcohol described inExperimental Chemistry Course, vol. 23, Fourth edition (edited by TheChemical Society of Japan) or the like.

(Step 3)

According to the same method as the third step of the Method A, acompound (viii) can be obtained from the compound (vii).

wherein Hal⁸ is halogen; R⁴³ is a group represented by the formula:R⁴⁴(R⁴⁵O)N wherein R⁴⁴ and R⁴⁵ are independently C1-C3 ally or a grouprepresented by the formula:

wherein W² is a non-aromatic nitrogen-containing heterocyclic group; R⁴⁶is C1-C3 alkyl or a group represented by the formula:

wherein L¹ is C2-C3 alkylene;R¹, R², R⁵, R⁶, and R⁷ are as defined in (1)(Step 1)

The first step is a step of obtaining a compound (x) by reacting thecompound (iii) obtained in the A method with an alcohol or a reagentrepresented by the formula:

wherein L¹ is C2-C3 alkylene while carbon monoxide is inserted in thepresence of a palladium catalyst.

The compound (x) can be obtained by reacting the compound (iii) with analcohol such as methanol, ethanol, n-propanol, isopropanol and the like,or a reagent such as N-hydroxysuccinic acid imide and the like at 50° C.to 150° C., preferably 70° C. to 90° C. under the carbon monoxideatmosphere in a solvent such as N,N-dimethylformamide,N,N-dimethylacetamide, N,N′-dimethylimidazolidinone, dimethyl sulfoxideand the like in the presence of a palladium catalyst such asdichlorobis(triphenylphosphine)palladium,tetrakis(triphenylphosphine)palladium,tris(dibenzylideneacetone)dipalladium,[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium, palladiumacetate+triphenylphosphine, palladiumacetate+1,3-bisdiphenylphosphinopropane and the like, and a base such astriethylamine, di(isopropyl)ethylamine and the like.

(Step 2)

The second step is a step of obtaining a compound (xi) by reacting thecompound (x) with a reagent represented by the formula: R⁴⁴ (R⁴⁵O)NHwherein R⁴⁴ and R⁴⁵ are independently C1-C3 alkyl or a reagentrepresented by the formula:

wherein W² is a non-aromatic nitrogen-containing heterocyclic group.

The compound (xi) can be obtained by mixing the compound (x) with areagent represented by the formula: R⁴⁴(R⁴⁵O)NH wherein R⁴⁴ and R⁴⁵ areindependently C1-C3 alkyl or a reagent represented by the formula:

wherein W² is a non-aromatic nitrogen-containing heterocyclic group in asolvent such as tetrahydrofuran, N,N-dimethylformamide, chloroform,dichloromethane and the like, and adding a reagent such asmethylmagnesium chloride, methylmagnesium bromide, isopropylmagnesiumchloride, methyllithium and the like at −100° C. to 50° C., preferably−78° C. to 20° C. to react them(Step 3)

The third step is a step of reacting the compound (xi) with a reagentrepresented by the formula: R²M wherein M is Li, Na, K, or a grouprepresented by the formula: MgHal⁵ wherein Hal⁵ is halogen; R² is asdefined in (1) to obtain a compound (vii).

The compound (vii) can be obtained by reacting the compound (xi) with areagent represented by the formula: R²M wherein M is Li, Na, K, or agroup represented by the formula: MgHal⁵ wherein Hal⁵ is halogen; R² isas defined in (1) at −100° C. to 50° C., preferably −78° C. to 20° C. ina solvent such as tetrahydrofuran, diethyl ether, toluene, n-hexane andthe like.

(Step 4)

According to the same manner as the third step of the Method A, acompound (viii) can be obtained from the compound (vii).

As an alternative method for the first step and the second step ofMethod E, there is following Method E′.

Wherein Hal⁸ and R⁴³ are as defined above; R⁵, R⁶, and R⁷ re as definedin (1).(Step 1)

The first step is a step of obtaining a compound (xi) by reacting thecompound (iii) with a reagent represented by the formula: R⁴³H whereinR⁴³ is as defined above while carbon monoxide is inserted in thepresence of a palladium catalyst.

By reacting a reagent represented by R⁴³H wherein R⁴³ is as definedabove in place of an alcohol or the like according to the same manner asthat of the first step of the Method E, the compound (xi) can beobtained from the compound (iii).

As another method of obtaining an amide derivative (xi) of method E,there is following Method E″.

Wherein Hal⁶ s halogen; Hal⁷ is halogen; R⁴³ and R⁴⁶ are as definedabove; R⁵, R⁶, and R⁷ are as defined in (1).(Step 1)

According to the same manner as that of the first step of the Method E,a compound (xii) can be obtained from a compound (xvi).

(Step 2)

According to the same manner as that of the second step of Method E, acompound (xiii) can be obtained from the compound (xii).

(Step 3)

The third step is a step of converting a hydroxyl group of the compound(xiii) into halogen to obtain a compound (xiv).

The compound (xiv) can be obtained by reacting the compound (xiii) witha halogenating agent such as phosphorus oxychloride, phosphorusoxybromide and the like at 00° C. to 200° C., preferably 200° C. to 150°C. in a solvent such as toluene, tetrahydrofuran and the like in thepresence of a base such as triethylamine, diisopropylethylamine,pyridine and the like.

(Step 4)

According to the same manner as that of the first step of Method A, acompound (xi) can be obtained from the compound (xiv).

The present compound (I) in which A is a group represented by theformula:

wherein Y² is a single bond or C1-C3 alkylene; R⁶, R⁷, and R⁸ are asdefined in (1) can be also synthesized by the following Method F.

Wherein Hal⁶ and Hal⁷ are halogen; Y² is a single bond or C1-C3alkylene; Pg is a suitable protecting group for a hydroxyl group; R¹,R², R⁶, R⁷, and R⁸ are as defined in (1); R⁴³ and R⁴⁶ are as definedabove.(Step 1)

According to the same manner as that of the first step of Method A, acompound (iii′) can be obtained from a starting compound (S.M.) and acompound (ii′).

(Step 2)

The second step is a step of binding a protecting group to a hydroxylgroup of the compound (iii′) to synthesize a compound (iii″).

A suitable protecting group may be bound by the method described inProtective Groups in Organic Synthesis, Theodora W Green (John Wiley &Sons) or the like.

(Step 3)

According to the same manner as that of the first step of Method E, acompound (x′) can be obtained from the compound (iii″).

(Step 4)

According to the same manner as that of the second step of Method E, acompound (xi′) can be obtained from the compound (x′).

(Step 5)

According to the same manner as that of the third step of Method E, acompound (vii′) can be obtained from the compound (xi′).

(Step 6)

According to the same manner as that of the third step of Method A, acompound (viii′) can be obtained from the compound (vii′).

(Step 7)

The seventh step is a step of removing a protecting group of thecompound (viii′) to synthesize a compound (viii″).

Deprotection may be performed under the suitable condition by the methoddescribed in Protective Groups in Organic Synthesis, Theodora W Green(John Wiley & Sons) or the like.

(Step 8)

The eighth step is a step of reacting the compound (viii″) with areagent represented by the formula: R⁸—Y²-Hal⁸ wherein Hal⁸ is halogen;Y² is a single bond or C1-C3 alkylene; R⁸ is as defined in (1) to obtaina compound (viii′″).

The compound (viii′″) can be obtained by reacting the compound (viii″)with a reagent represented by the formula: R⁸—Y²-Hal⁸ wherein Hal⁸ ishalogen; Y² is a single bond or C1-C3 alkylene; R⁸ is as defined in (1)at −20° C. to 200° C., preferably 0° C. to 100° C. in a solvent such asN,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, diethylether, toluene, n-hexane and the like in the presence of a base such ascesium carbonate, potassium carbonate, sodium carbonate, lithiumcarbonate, potassium bicarbonate, sodium bicarbonate, potassiumhydroxide, sodium hydroxide, triethylamine, pyridine and the like.

As Y² in Method F, C1-C3 alkylene is preferable. Particularly, methyleneis preferable.

As R⁸ in Method F, phenyl optionally substituted with halogen, orpyridyl optionally substituted with halogen is preferable.

An alkoxyamine reagent represented by the formula: R—O—NH₂ wherein R¹ isas defined in (1) used in the third step of Method A is commerciallyavailable, or can be synthesized using, as a starting raw material, analcohol compound which can be synthesized according to the methoddescribed in J. Med. Chem., 1999, 42:2007-2020, Liebigs Ann. Chem.,1988:1149-1153, Organic Letters, 2004, 6:4069-4072, Organic Letters,2005, 7:937-939, WO 04/054514 or the like, according to the methoddescribed in WO 02/062313 or the like.

In the compound represented by the formula (I), compounds represented bythe following formula (I-A) to formula (I-P) are preferable.

A compound represented in the formula (I-A):

wherein R²¹ is alkyl substituted with amino optionally substituted witha substituent selected from substituent group C consisting of alkyl,alkenyl, alkynyl, optionally substituted aryl, araklyl, alkyloxy,hydroxyalkyl, hydroxyalkyloxyalkyl, haloalkyl, aminoalkyl optionallysubstituted with 1 or 2 alkyl(s), alkylsulfonyl, alklysulfonylalkyl,alkylcarbonyl optionally substituted with halogen or alkyloxy,alkyloxycarbonyl, optionally substituted cycloalkyl, carboxyalkyl,optionally substituted aminocarbonylalkyl, optionally substitutedaminocarbonyloxyalkyl, alkyloxyalkyl, alkylthioalkyl,alkylcarbonylaminoalkyl, alkylsulfonylaminoalkyl,alkylsulfonyl(alkyl)aminoalkyl, alkyloxycarbonylalkyl,alkylthio(hydroxy)alkyl, cycloalkylalkyl, cyanoalkyl, optionallysubstituted aminoalkylcarbonyl, optionally substituted heteroaryl,heteroarylalkyl, hydroxyalkyloxyalkyl, optionally substitutednon-aromatic heterocyclic group, and optionally substituted non-aromaticheterocyclic alkyl; alkyl substituted with a non-aromaticnitrogen-containing heterocyclic group, wherein the non-aromaticnitrogen-containing heterocyclic group is selected from pyrrolidinyl,piperidyl, piperazinyl, morpholinyl, and thiomorpholinyl, optionallysubstituted with a substituent selected from substituent group Dconsisting of halogen; aryl; hydroxy; oxo; optionally substitutedaminocarbonyl; alkyloxycarbonyl; alkyl optionally substituted with asubstituent selected from substituent group H consisting of optionallysubstituted aminocarbonyl, cyano, alkyloxy, alkylsulfonylamino, amino,carboxy, alkyloxycarbonyl, and hydroxy; alkylaminocarbonyl; carboxy;cyano, alkylsulfonyl; alkylcarbonyl; alkenylcarbonyl;alkylsulfonylalkylcarbonyl; alkyloxyalkylcarbonyl; alkylcarbonylamino;aminocarbonyloxy; a non-aromatic nitrogen-containing heterocyclic group;and non-aromatic heterocyclic carbonyl; or a non-aromaticnitrogen-containing heterocyclic group, wherein the non-aromaticnitrogen-containing heterocyclic group is selected from azetidinyl,pyrrolidinyl, and piperidyl, optionally substituted with a substituentselected from substituent group B consisting of alkyloxycarbonyl,optionally substituted aminocarbonyl, oxo, amino, carboxy, cyano,cyanoalkyl, hydroxyalkyl, alkylcarbonylamino, alkylsulfonylamino, andaminocarbonylalkyl; R²² is alkyl optionally substituted with asubstituent selected from substituent group K consisting of aminooptionally substituted with alkyl, hydroxy, alkyloxy, and halogen;alkenyl optionally substituted with a substituent selected fromsubstituent group K, alkynyl optionally substituted with a substituentselected from substituent group K; hydroxy; halogen; phenyl; pyridyl;furyl; thienyl; or thiazolyl;one of R²³ and R²⁴ is a hydrogen atom, and the other is a hydrogen atom,alkyloxy, alkyloxyalkyloxy, halogen, or aminoalkyl optionallysubstituted with alkyl,R²⁷ is a hydrogen atom, alkyl, or acyl; andR²⁵ and R²⁶ are each independently a hydrogen atom, halogen, alkynyl,hydroxy, alkyloxy, alkenyloxy, alkynyloxy, or heteroarylalkyloxy, itspharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-B):

wherein R²¹, R²², R²³, R²⁴ and R²⁷ are as defined above;Y¹ is C1-C3 alkylene;R²⁸ is alkyl, alkyloxy, alkynyl, or halogen; andR²⁹, R³⁰, and R³¹ are each independently a hydrogen atom or asubstituent selected from substituent group F consisting of halogen,carboxy, alkyl, haloalkyl, hydroxyalkyl, alkyloxy, alkyloxycarbonyl, andoptionally substituted amino,its pharmaceutically acceptable salt, or a solvate thereof

A compound represented by the formula (I-C):

wherein R²¹, R²², R²³, R²⁴, and R²⁷ are as defined above;R³⁵ is alkyl optionally substituted with a substituent selected fromsubstituent group L consisting of hydroxy, alkyloxy, halogen, and cyano;alkenyl optionally substituted with a substituent selected fromsubstituent group L; alkynyl optionally substituted with a substituentselected from substituent group L; or a group represented by theformula:

wherein R²¹, R³⁰, and R³¹ are as defined above;Q is N or CH₂,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-D):

wherein R²¹, R²²R²³, R²⁴, R²⁵, R²⁶, and R²⁷ are as defined above; andR³⁶ is alkyl substituted with aminocarbonyl optionally substituted witha substituent selected from substituent group C oralkyl substituted with non-aromatic heterocyclic carbonyl, wherein thenon-aromatic nitrogen-containing heterocycle is selected frompyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, andthiomorpholinyl, optionally substituted with a substituent selected fromsubstituent group D,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-E):

wherein R²¹, R²², R²³, R²⁴, R²⁷, R²⁸, R²⁹, R³⁰, R³¹, R³⁶, and Y¹ are asdefined above,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-F):

wherein R²², R²³, R²⁴, R²⁷, R³⁶, and Q are as defined above,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-G):

wherein R²³, R²⁴, R²⁵, R²⁶, and R²⁷ are as defined above;R³² is alkyl substituted with amino optionally substituted with asubstituent selected from substituent group C,alkyl substituted with a non-aromatic nitrogen-containing heterocyclicgroup, wherein the non-aromatic nitrogen-containing heterocyclic groupis selected from pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, andthiomorpholinyl, optionally substituted with a substituent selected fromsubstituent group D, or a non-aromatic nitrogen-containing heterocyclicgroup, wherein the non-aromatic nitrogen-containing heterocyclic groupis selected from azetidinyl, pyrrodilinyl, and piperidyl, optionallysubstituted with a substituent selected from substituent group B,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-H):

wherein R²³, R²⁴, R²⁷, R²⁸, R²⁹, R³⁰, R³¹, R³², and Y¹ are as definedabove, its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-I):

wherein R²³, R²⁴R²⁷, R³², R³⁵, and Q are as defined above,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-J):

wherein R²², R²³, R²⁴, R²⁵, R²⁵, and R²⁷ are as defined above;W² is pyrrolidinyl optionally substituted with a substituent selectedfrom substituent group J, piperidyl optionally substituted with asubstituent selected from substituent group J, piperazinyl optionallysubstituted with a substituent selected from substituent group J,morpholinyl optionally substituted with a substituent selected fromsubstituent group J, or triazolyl optionally substituted with asubstituent selected from substituent group J, its pharmaceuticallyacceptable salt, or a solvate thereof.

A compound represented by the formula (I-K):

wherein R²², R²³, R²⁴, R²⁷, R²⁸, R²⁹, R³⁰, R³¹, Y¹, and W² are asdefined above,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-L):

wherein R²², R²³, R²⁴, R²⁷, R³⁵, W², and Q are as defined above,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (IM):

wherein R²², R²³, R²⁴, R²⁵, R²⁶, and R²⁷ are as defined above;R³³ is a hydrogen atom, C1-C6 alkyl optionally substituted with asubstituent selected from substituent group L, C2-C6 alkenyl optionallysubstituted with a substituent selected from substituent group L, orC2-C6 alkynyl optionally substituted with a substituent selected fromsubstituent group L; andR³⁴ is alkyl substituted with amino optionally substituted with asubstituent selected from substituent group C, alkyl substituted with anon-aromatic nitrogen-containing heterocyclic group optionallysubstituted with a substituent selected from substituent group D, aryloptionally substituted with a substituent selected from substituentgroup F, heteroaryl optionally substituted with a substituent selectedfrom substituent group F, or a non-aromatic heterocyclic groupoptionally substituted with a substituent selected from substituentgroup F,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-N):

wherein R²², R²³, R²⁴, R²⁷, R²⁸, R²⁹, R³⁰, R³¹, R³³, R³⁴, and Y¹ are asdefined above,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-O):

wherein R²², R²³, R²⁴, R²⁷, R³⁴, R³⁵, and Q are as defined above,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-P):

wherein R³⁷ is alkyl substituted with amino optionally substituted withalkyl, hydroxyalkyl, alkylcarbonylaminoalkyl or a non-aromaticheterocyclic group; alkyl substituted with a non-aromaticnitrogen-containing heterocyclic group optionally substituted withalkyl, hydroxyalkyl or alkylcarbonylamino; or a non-aromaticnitrogen-containing heterocyclic group substituted with hydroxyalkyl;R³⁸ is C2-C4 alkynyl;R³⁹ is halogen;R⁴⁰ is a group represented by the formula: —Y³—R⁴² wherein Y³ isalkylene which may be intervened with —O—; R⁴² is phenyl optionallysubstituted with halogen, or pyridyl optionally substituted withhalogen;R⁴¹ is halogen;Y¹ is as defined above,its pharmaceutically acceptable salt, or a solvate thereof.

A compound represented by the formula (I-Q):

wherein R⁴⁷ is a group represented by the formula:

R³⁷ is as defined above,its pharmaceutically acceptable salt, or a solvate thereof.

As R²² in compounds represented by the formula (I-A) to the formula(I-F) and the formula (I-J) to the formula (I-O), methyl, ethyl,n-propyl, isopropyl, propynyl, butynyl, or phenyl is preferable.

Herein, the “solvate” includes, for example, a solvate with an organicsolvent, a hydrate and the like. When a solvate is formed, the compoundmay be coordinated with an arbitrary number of water molecules.

When referred to the “present compound”, a pharmaceutically acceptablesalt, and a hydrate thereof are also included. Examples include salts ofalkali metals (lithium, sodium, potassium etc.), or alkaline-earthmetals (magnesium, calcium etc.), and ammonium, organic bases and aminoacid, and salts with inorganic acids (hydrochloric acid, hydrobromicacid, phosphoric acid, sulfuric acid etc.), or organic acids (aceticacid, citric acid, maleic acid, fumaric acid, benzenesulfonic acid,p-toluenesulfonic acid etc.). These salts can be formed by methods whichare usually performed.

In addition, the present compound is not limited to specified isomers,but includes all possible isomers and racemates.

The present compound, as described in Experiment Examples describedlater, exhibits the excellent cell proliferation inhibiting activity,and can be used as an “pharmaceutical composition useful for treatingcancer” and a “therapeutic for a cancer”.

When the present compound is administered to a human for the purpose oftreating the aforementioned diseases, it can be orally administered aspowders, granules, tablets, capsules, pills, solutions or the like, orparenterally administered as injectables, suppositories, transdermalabsorbing agents, inhalants or the like. And, an effective amount of thepresent compound is mixed, if necessary, with pharmaceutical additivessuch as excipients, binders, wetting agents, disintegrating agents,lubricants and the like which are suitable for a dosage form, thereby,the present compound can be formulated into pharmaceutical preparations.In the case of injectables, the present compound together with asuitable carrier is subjected to sterilization treatment to obtainpreparations.

A dose is different depending on the condition of a disease, anadministration route, and an age or a weight of a patient, and isusually 0.1 to 100 mg/kg/day, preferably 1 to 20 mg/kg/day when orallyadministered to an adult.

The following Examples and Test Examples illustrate the presentinvention in more detail below, but the present invention is not limitedby them.

In Examples, following abbreviations are used.

Me: methyl

Et: ethyl

nPr: n-propyl

iPr: isopropyl

Ph: phenyl

EXAMPLES Example 1

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-iodoquinazoline (III-1)hydrochloride

In 180 ml of tetrahydrofuran were dissolved 4-chloro-6-iodoquinazoline(6.0 g) and 3-chloro-4-(3-fluorobenzyloxy)aniline (II-1, 5.2 g),followed by heat refluxing for 3 hours. A precipitate was filtered, andwashed with tetrahydrofuran to obtain4-(4-(3-fluorobenzyloxy)phenylamino)-6-iodoquinazoline hydrochloride(III-1, 10.5 g) as a yellow solid.

¹H NMR (d₆-DMSO 6): 11.47 (1H, brs), 9.25 (1H, s), 8.94 (1H, s), 8.36(1H, dd, J=1.8 Hz, J=8.7 Hz), 7.92 (1H, d, J=2.7 Hz), 7.71 (1H, d, J=8.7Hz), 7.66 (1H, dd, J=2.7 Hz, J=8.7 Hz), 7.48 (1H, dt, J=6.0 Hz, J=7.8Hz), 7.37-7.30 (3H, m), 7.19 (1H, dt, J=2.7 Hz, J=8.7 Hz), 5.30 (2H, s).

The following compound was synthesized according to the same method asthat of the above first step.

TABLE 1 [Chemical formula 59] (III)

Com- pound No. R^(A) ¹H-NMR(d₆-DMSO) III-2 —F 9.86 (1H, s), 8.95 (1H, d,J = 1.5 Hz), 8.61 (1H, s), 8.11 (1H, dd, J = 1.8 Hz, J = 8.7 Hz), 7.89(1H, J = 2.4 Hz, J = 13.5 Hz), 7.60-7.49 (2H, m), 7.45 (1H, dd, J = 6.3Hz, J = 8.1 Hz), 7.36-7.23 (3H, m), 7.19 (1H, dt, J = 8.4 Hz, J = 2.1Hz), 5.22 (2H, s). III-3 —OMe 11.26 (1H, brs), 9.18 (1H, s), 8.89 (1H,s), 8.34 (1H, dd, J = 1.5 Hz, J = 8.7 Hz), 7.66 (1H, d, J = 8.7 Hz),7.46 (1H, dt, J = 6.3 Hz, J = 8.1 Hz), 7.39 (1H, d, J = 2.1 Hz),7.34-7.25 (3H, m), 7.22-7.13 (1H, m), 7.13 (1H, d, J = 8.7 Hz), 5.17(2H, s), 3.82 (3H, s).

(Step 2) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-formylquinazoline (IV-1)

In 100 ml of dimethylformamide was dissolved4-(4-(3-fluorobenzyloxy)phenylamino)-6-iodoquinazoline hydrochloride(III-1, 5.0 g), and 1.25 g of sodium formate,dichlorobis(triphenylphosphine)palladium (324 mg), and triethylamine(3.2 ml) were added. The reaction mixture was degassed, and stirredunder heating at 80° C. for 3 hours under the carbon monoxideatmosphere. Thereafter, the reaction mixture was poured into ice water,and extracted with ethyl acetate. The extract was washed with water andsodium chloride solution, and dried with magnesium sulfate. The driedsolution was filtered with Celite, concentrated, and powdered with anethyl acetate-hexane (1:2) to obtain4-(4-(3-fluorobenzyloxy)phenylamino)-6-formylquinazoline (IV-1, 2.86 g)as a yellow solid.

¹H NMR (d₆-DMSO δ): 10.24 (1H, s), 10.13 (1H, s), 9.16 (1H, s), 8.69(1H, s), 8.27 (1H, br d, J=8.7 Hz), 8.03 (1H, d, J=2.1 Hz), 7.90 (1H, d,J=9.0 Hz), 7.74 (1H, dd, J=2.7 Hz, J=8.7 Hz), 7.48 (1H, dt, J=6.0 Hz,J=8.4 Hz), 7.36-7.30 (2H, m), 7.30 (1H, d, J=8.7 Hz), 7.19 (1H, br t,J=8.7 Hz), 5.27 (2H, s).

The following compound was synthesized according to the same method asthat of the above second step.

TABLE 2 [Chemical formula 60] (IV)

Com- pound No. R^(A) ¹H-NMR(d₆-DMSO) IV-2 —F 10.24 (1H, s), 10.14 (1H,s), 9.16 (1H, s), 8.69 (1H, s), 8.26 (1H, dd, J = 1.5 Hz, J = 8.7 Hz),7.94-7.85 (2H, m), 7.55 (1H, br d, J = 9.0 Hz), 7.47 (1H, dt, J = 6.3Hz, J = 8.1 Hz), 7.36-7.26 (3H, m), 7.23-7.15 (1H, m), 5.23 (2H, s).IV-3 —OMe 10.13 (2H, s), 9.18 (1H, s), 8.64 (1H, s), 8.25 (1H, dd, J =1.5 Hz, J = 8.7 Hz), 7.88 (1H, d, J = 8.4 Hz), 7.52-7.38 (3H, m),7.34-7.26 (2H, m), 7.22-7.12 (1H, m), 7.07 (1H, d, J = 8.7 Hz), 5.14(2H, s), 3.83 (3H, s).

(Step 3) Synthesis of 4-(3chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(1-piperidyl)ethoxyimino)quinazoline(V-1)

In a mixture of tetrahydrofuran (2 ml) and water (0.1 ml) were dissolved4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-formylquinazoline (IV-1,50 mg) and 2-(1-piperidyl)ethoxyamine dihydrochloride (36.5 mg), and themixture was stirred at room temperature overnight. The reaction mixturewas diluted with ethyl acetate, washed sequentially with aqueoussaturated sodium bicarbonate solution, and aqueous sodium chloridesolution, and dried over magnesium sulfate. After concentration, theresidue was purified by chromatography (eluting with hexane:ethylacetate=2:3) using an amino column, and further re-purified by thinlayer chromatography to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(1-piperidyl)ethoxyimino)_(q)quinazoline (V-1, 13 mg).

¹H NMR (d₆-DMSO, δ): 9.95 (1H, s), 8.63 (1H, s), 8.59 (1H, s), 8.34 (1H,s), 8.10 (1H, d, J=9.3 Hz), 8.00 (1H, d, J=2.4 Hz), 7.79 (1H, d, J=8.7Hz), 7.72 (1H, dd, J=9.0 Hz, J=2.1 Hz), 7.51-47.4 (1H, m), 7.36-7.31(2H, m), 7.28 (1H, d, J=9.0 Hz), 7.19 (1H, br t, J=9.0 Hz), 5.26 (2H,s), 4.28 (2H, t, J=6.0 Hz), 2.63 (2H, t, J=6.0 Hz), 2.41 (4H, t, J=4.8Hz), 1.50 (4H, quin, J=5.3 Hz), 1.45-1.35 (2H, m).

Example 2

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(N-(t-butoxycarbonyl)-N-ethylamino)ethyloxyimino)quinazoline(V-16)

In tetrahydrofuran (1.5 ml) were dissolved4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-formylquinazoline (IV-1,120 mg) and N-(t-butoxycarbonyl)ethylaminoethoxyamine (110 mg), and 134μl of 2 mol/L hydrochloric acid was added, then the mixture was stirredat room temperature for 4 hours. After completion of the reaction, thereaction mixture was poured into aqueous ice-cooled saturated sodiumbicarbonate solution, and extracted with ethyl acetate. The organiclayer was washed with water and aqueous sodium chloride solution, driedover magnesium sulfate, and concentrated. The resulting residue waspurified by amino column chromatography (eluting with hexane:ethylacetate=1:1), and further re-purified by silica gel chromatography(eluting with hexane:ethyl acetate=1:1) to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(N-(t-butoxycarbonyl)-N-ethylamino)ethyloxyimino)quinazoline(V-16, 96 mg) as a yellow viscous oil.

¹H NMR (d₆-DMSO, δ): 9.93 (1H, s), 8.63 (1H, brs), 8.60 (1H, s), 8.34(1H, s), 8.12 (1H: dd, J=1.2 Hz, J=9.0 Hz), 8.01 (1H, d, J=2.4 Hz), 7.79(1H, d, J=8.4 Hz), 7.72 (1H, dd, J=2.4 Hz, J=8.4 Hz), 7.48 (1H, dt,J=6.0 Hz, J=8.1 Hz), 7.36-7.30 (2H, m), 7.28 (1H, d, J=9.0 Hz),7.23-7.14 (1H, m), 5.26 (2H, s), 4.26 (2H, t, J=5.7 Hz), 3.50 (2H, t,J=63 Hz), 3.23 (2H, q, J=6.9 Hz), 1.38 (9H, s), 1.12-1.00 (3H, m).

The following compound was synthesized according to the same manner asthat of the above first step.

TABLE 3 [Chemical formula 62] (V)

Compound No. R^(A) R^(B) ¹H-NMR(d₆-DMSO) V-18 Cl

9.92 (1H, s), 8.62 (1H, s), 8.60 (1H, s), 8.34 (1H, s), 8.12 (1H, d, J =8.4 Hz), 8.00 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.7 Hz), 7.72 (1H,dd, J = 2.4 Hz, J = 8.7 Hz), 7.47 (1H, dt, J = 6.0 Hz, J = 7.8 Hz),7.36-7.30 (2H, m), 7.28 (1H, d, J = 9.0 Hz), 7.23-7.14 (1H, m), 5.26(2H, s), 4.28 (2H, t, J = 5.7 Hz), 3.57-3.48 (2H, m), 2.84 (3H, brs),1.36 (9H, s). V-19 Cl

9.92 (1H, s), 8.63 (1H, s), 8.60 (1H, s), 8.33 (1H, s), 8.12 (1H, dd, J= 1.5 Hz, J = 9.0 Hz), 8.01 (1H, d, J = 2.4 Hz), 7.80 (1H, d, J = 8.7Hz), 7.72 (1H, dd, J = 2.7 Hz, J = 9.0 Hz), 7.47 (1H, dt, J = 6.0 Hz, J= 7.8 Hz), 7.36-7.30 (2H, m), 7.28 (1H, d, J = 9.0 Hz), 7.22-7.14 (1H,m), 5.26 (2H, s), 4.21 (2H, t, J = 6.0 Hz), 3.8-3.5 (1H, brs), 3.48-3.37(2H, m), 1.8-1.4 (6H, m), 1.35-1.0 (4H, m). V-20 OMe

9.83 (1H, s), 8.64 (1H, s), 8.57 (1H, s), 8.34 (1H, s), 8.12 (1H, dd, J= 1.5 Hz, J = 8.7 Hz), 7.78 (1H, d, J = 8.7 Hz), 7.50-7.36 (3H, m),7.34-7.26 (2H, m), 7.21-7.13 (1H, m), 7.06 (1H, d, J = 8.7 Hz), 5.13(2H, s), 4.26 (2H, t, J = 5.7 Hz), 3.82 (3H, s), 3.50 (2H, t, J = 5.7Hz), 3.23 (2H, q, J = 7.2 Hz), 1.38 (9H, s), 1.12-1.02 (3H, m). V-21 OMe

9.84 (1H, s), 8.63 (1H, s), 8.56 (1H, s), 8.36 (1H, s), 8.12 (1H, dd, J= 1.5 Hz, J = 8.7 Hz), 7.77 (1H, d, J = 8.7 Hz), 7.50-7.35 (3H, m),7.33-7.25 (2H, m), 7.20-7.12 (1H, m), 7.05 (1H, d, J = 8.7 Hz), 5.13(2H, s), 4.27 (2H, t, J = 5.7 Hz), 3.82 (3H, s), 3.55-3.47 (2H, m), 2.84(3H, brs), 1.36 (9H, s). V-22 OMe

9.82 (1H, s), 8.64 (1H, s), 8.56 (1H, s), 8.33 (1H, s), 8.11 (1H, dd, J= 1.5 Hz, J = 8.7 Hz), 7.78 (1H, d, J = 8.7 Hz), 7.50-7.36 (3H, m),7.33-7.26 (2H, m), 7.21-7.12 (1H, m), 7.05 (1H, d, J = 8.7 Hz), 5.13(2H, s), 4.21 (2H, t, J = 6.6 Hz), 3.82 (3H, s), 3.8-3.5 (1H, m),3.47-3.35 (2H, m), 1.8-1.35 (6H, m), 1.41 (9H, s), 1.35-0.95 (4H, m).V-28 Cl

9.91 (1H, s), 8.62 (1H, brs), 8.60 (1H, s), 8.36 (1H, s), 8.10 (1H, dd,J = 8.7 Hz), 8.01 (1H, brs), 7.79 (1H, d, J = 8.4 Hz), 7.73 (1H, d, J =8.1 Hz), 7.52-7.44 (1H, m), 7.35-7.27 (3H, m), 7.19 (1H, dt, J = 8.1 Hz,J = 2.4 Hz), 5.26 (2H, s), 4.28 (1H, brs), 4.17 (1H, dd, J = 10.5 Hz, J= 6.9 Hz), 4.00 (1H, brs), 3.25 (3H, br), 1.92 (3H, br), 1.80 (1H, br),1.43 (9H, s)

(Step 2) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(N-ethylamino)ethyloxyimino)quinazoline(V-17)

In chloroform (1.8 ml) was dissolved4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(N-(t-butoxycarbonyl)-N-ethylamino)ethyloxyimino)quinazoline(V-16, 54 mg), and trifluoroacetic acid (1.8 ml) was added, followed bystirring at room temperature for 1 hour. After completion of thereaction, the reaction mixture was concentrated, and diluted with ethylacetate. The mixture was sequentially washed with aqueous saturatedsodium bicarbonate solution, water, and aqueous sodium chloritesolution, and dried over magnesium sulfate. After concentration, thecrystalline residue was washed with a mixture of dichloromethane-hexane(1:4) to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(N-ethylamino)ethyloxyimino)quinazoline(V-17, 28 mg) as a white solid.

¹H NMR (d₆-DMSO, δ): 9.96 (1H, s), 8.65 (1H, brs), 8.60 (1H, s), 8.35(1H, s), 8.11 (1H, d, J=9.0 Hz), 8.01 (1H, J=3.0 Hz), 7.80 (1H, d, J=9.0Hz), 7.75-7.70 (1H, m), 7.52-7.43 (1H, m), 7.36-7.31 (2H, m), 7.28 (1H,d, J=9.3 Hz), 7.23-7.14 (1H, m), 5.26 (2H, s), 4.26 (2H, t, J=6.0 Hz),2.03 (2H, t, J=6.0 Hz), 2.66 (2H, q, J=7.2 Hz), 1.05 (3H, t, J=7.2 Hz).

Example 3

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(N-cyanomethylpyrrolidin-2-yl)methoxyimino)methylquinazoline(V-30)

In 0.4 mL of N,N-dimethylacetamide were dissolved 40 mg of Compound V-29and 8 μL of iodoacetonitrile, and 15 mg of potassium carbonate wasadded, followed by stirring at room temperature for 1 hour. After thereaction, aqueous saturated sodium chloride solution was added, followedby extraction with ethyl acetate. The organic layer was dehydrated bypassing through Presep (registered trademark), and the filtrate wasconcentrated. The concentrated residue was purified by silica gelchromatography (eluting with hexane:ethyl acetate=2:1) to obtain 35 mgof 4-(3-chloro-4(3-fluorobenzyloxy)phenylamino)-6-(1-(N-cyanomethylpyrrolidin-2-yl)methoxyimino)methylquinazoline(V-30).

¹H NMR (d₆-DMSO, δ): 9.92 (1H, s), 8.62 (1H, d, J=1.5 Hz), 8.58 (1H, s),8.36 (1H, s), 8.00 (1H, dd, J=8.7 Hz, J=1.5 Hz), 7.99 (1H, d, J=2.6 Hz),7.78 (1H, d. J=8.7 Hz), 7.71 (1H, dd, J=9.0 Hz, J=2.6 Hz), 7.49-7.42(1H, m), 7.33-7.25 (3H, m), 7.16 (1H, dt. J=8.1 Hz, J=1.8 Hz), 5.24 (2H,s), 4.17 (2H, d, J=5.7 Hz), 3.97 (1H, d, J=1.7 Hz), 3.90 (1H, J=17 Hz),3.00-2.89 (2H, m), 2.01-1.89 (1H, m), 1.78-1.54 (3H, m).

Example 4

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(4-acryloyl-1-piperazin-1-yl)ethoxyimino)methylquinazoline(V-43)

In 1.5 mL of tetrahydrofuran were dissolved 40 mg of Compound V-42 and 6μL of acryloyl chloride, followed by stirring at room temperature for 2hours. After the reaction, aqueous saturated sodium, chloride solutionwas added, followed by extraction with ethyl acetate. The organic layerwas dehydrated by passing through CHEM ELUT (trade name), and thefiltrate was concentrated. The concentrated residue was purified bychromatography (eluting with 1% methanol-containing ethyl acetate), andthe resulting residue was solidified with hexane-ethyl acetate (6:1) toobtain 20 mg of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(4-acryloyl-1-piperazin-1-yl)ethoxyimino)methylquinazoline(V-43).

¹H NMR (d₆-DMSO, δ): 9.95 (1H, s), 8.64 (1H, s), 8.59 (1H, s), 8.35 (1H,s), 8.10 (1H, d, J=8.7 Hz), 8.00 (1H, d, J=2.4 Hz), 7.78 (1H, d, J=8.7Hz), 7.72 (1, dd, J=9.0 Hz, 2.7 Hz), 7.44-7.51 (1H, m), 7.26-7.35 (3H,m), 7.15-7.22 (1H, m), 6.79 (1H, dd, J=16.5 Hz, 10.2 Hz), 6.10 (1H, dd,J=16.5 Hz, 2.4 Hz), 6.17 (1H, dd, J=10.5 Hz, 2.4 Hz), 5.26 (2H, s), 4.32(2H, t, J=5.7 Hz), 3.55 (4H, m), 2.72 (2H, t, J=5.7 Hz), 2.50 (4H, m)

Example 5

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(4-(2-methanesulfonylethyl)-1-piperazin-1-yl)ethoxyimino)methylquinazoline(V-44)

In 1 mL of tetrahydrofuran were dissolved 25 mg of Compound V-42 and 4μL of methylvinylsulfone, followed by stirring at room temperature for21 hours. Further, 4 μL of methylvinylsulfone was added, followed bystirring at room temperature for 29 hours. After the reaction, aqueoussaturated sodium chloride solution was added, followed by extractionwith ethyl acetate. The organic layer was washed sequentially withwater, and aqueous saturated sodium chloride solution, and dried overmagnesium sulfate. The concentrated residue was purified bychromatography (eluting with ethyl acetate) using an amino column, andthe resulting residue was solidified with hexane-ethyl acetate (6:1) toobtain 15 mg of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(4-(2-methanesulfonylethyl)-1-piperazin-1-yl)ethoxyimino)methylquinazoline(V-44).

¹H NMR (d₆-DMSO, δ): 9.95 (1H, s), 8.63 (1H, s), 8.59 (1H, s), 8.34 (1H,s), 8.10 (1H, d, J-9.6 Hz), 8.00 (1H, d, J=2.4 Hz), 7.79 (1H, d, J=8.4Hz), 7.71 (1H, dd, J=8.7 Hz, 2.7 Hz), 7.44-7.51 (1H, m), 7.26-7.34 (3H,m), 7.15-7.22 (1H, m), 5.26 (2H, s), 4.29 (2H, t, J=6.0 Hz), 3.27 (2H,t, J=6.6 Hz), 3.02 (3H, s), 2.67-2.70 (4H, m), 2.46 (8H, m)

The following compound was synthesized according to the same methods asthat of Examples 1 to 5.

TABLE 4 [Chemical formula 66] (V)

Compound No. R^(A) R^(B) ¹H-NMR(d₆-DMSO) V-2 Cl

11.69 (1H, s), 11.11 (1H, brs), 8.84 (1H, s), 8.83 (1H, s), 8.29 (1H,s), 8.26 (1H, d, J = 8.7 Hz), 7.95 (1H, d, J = 2.7 Hz), 7.88 (1H, d, J =8.7 Hz), 7.67 (1H, dd, J = 2.3 Hz, J = 9.2 Hz), 7.48 (1H, dt, J = 6.0Hz, J = 7.8 Hz), 7.37-7.29 (3H, m), 7.20 (1H, br t, J = 9.2 Hz), 5.30(2H, s). V-3 Cl

9.96 (1H, s), 8.65 (1H, s), 8.60 (1H, s), 8.34 (1H, s), 8.10 (1H, br d,J = 8.7 Hz), 8.01 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.4 Hz), 7.73(1H, dd, J = 2.7 Hz, J = 9.0 Hz), 7.48 (1H, dt, J = 6.0 Hz, J = 8.1 Hz),7.36-7.31 (2H, m), 7.28 (1H, d, J = 9.0 Hz), 7.19 (1H, br t, J = 8.7Hz), 5.26 (2H, s), 3.98 (3H, s). V-4 Cl

9.95 (1H, s), 8.63 (1H, s), 8.60 (1H, s), 8.36 (1H, s), 8.10 (1H, dd, J= 8.7 Hz, J = 1.2 Hz), 8.01 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.4Hz), 7.72 (1H, dd, J = 2.6 Hz, J = 8.9 Hz), 7.48 (1H, dt, J = 6.0 Hz, J= 8.1 Hz), 7.36-7.29 (2H, m), 7.28 (1H, d, J = 9.0 Hz), 7.19 (1H, dt, J= 2.4 Hz, J = 8.6 Hz), 5.27 (2H, s), 3.97 (2H, d, J = 6.9 Hz), 2.05 (1H,m), 0.95 (6H, d, J = 6.9 Hz). V-5 Cl

9.96 (1H, s), 8.64 (1H, s), 8.60 (1H, s), 8.39 (1H, s), 8.11 (1H, dd, J= 1.5 Hz, J = 8.7 Hz), 8.01 (1H, d, J = 2.7 Hz), 7.79 (1H, d, J = 8.7Hz), 7.72 (1H, dd, J = 2.7 Hz, J = 9.0 Hz), 7.48 (1H, dt, J = 6.3 Hz, J= 7.8 Hz), 7.36-7.29 (2H, m), 7.28 (1H, d, J = 9.0 Hz), 7.19 (1H, dt, J= 2.2 Hz, J = 8.6 Hz), 6.08 (1H, ddt, J = 17.4 Hz, J = 10.5 Hz, J = 5.7Hz), 5.38 (1H, ddd, J = 17.4 Hz, J = 3.6 Hz, J = 1.8 Hz), 5.30-5.24 (1H,m), 5.26 (2H, s), 4.72 (2H, dt, J = 5.7 Hz, J = 1.5 Hz). V-6 Cl

9.95 (1H, s), 8.64 (1H, s), 8.60 (1H, s), 8.35 (1H, s), 8.11 (1H, br d,J = 8.7 Hz), 8.00 (1H, d, J = 2.7 Hz), 7.79 (1H, d, J = 8.7 Hz), 7.72(1H, dd, J = 2.7 Hz, J = 9.0 Hz), 7.51-7.44 (1H, m), 7.36-7.31 (2H, m),7.28 (1H, d, J = 9.3 Hz), 7.19 (1H, br t, J = 8.4 Hz), 5.26 (2H, s),4.29 (2H, t, J = 6.3 Hz), 2.810 (2H, t, J = 4.8 Hz), 2.6-2.5 (4H, m),1.75-1.65 (4H, m). V-7 Cl

9.95 (1H, s), 8.64 (1H, s), 8.60 (1H, s), 8.35 (1H, s), 8.11 (1H, dd, J= 8.7 Hz, J = 1.5 Hz), 8.01 (1H, d, J = 2.7 Hz), 7.80 (1H, d, J = 9.0Hz), 7.72 (1H, dd, J = 9.0 Hz, J = 2.7 Hz), 7.48 (1H, dt, J = 6.0 Hz, J= 8.1 Hz), 7.36-7.31 (2H, m), 7.28 (1H, d, J = 9.3 Hz), 7.19 (1H, br t J= 9.0 Hz), 5.27 (2H, s), 4.31 (2H, t, J = 5.7 Hz), 2.46 (4H, t, J = 4.5Hz).

TABLE 5 Compound No. R^(A) R^(B) ¹H-NMR(d₆-DMSO) V-8  —Cl

9.94 (1H, s), 8.63 (1H, s), 8.59 (1H, s), 8.33 (1H, s), 8.10 (1H, br d,J = 7.2 Hz), 8.00 (1H, d, J = 2.4 Hz), 7.78 (1H, d, J = 8.7 Hz), 7.71(1H, dd, J = 8.7 Hz, J = 2.1 Hz), 7.47 (1H, dt, J = 6.3 Hz, J = 8.1 Hz),7.36-7.31 (2H, m), 7.28 (1H, d, J = 9.0 Hz), 7.18 (1H, br t, J = 9.0Hz), 5.26 (2H, s), 4.23 (2H, t, J = 6.3 Hz), 3.57 (4H, t, J = 4.5 Hz),2.45-2.35 (6H, m), 1.87 (2H, quin, J = 6.8 Hz). V-9  —Cl

9.95 (1H, s), 8.63 (1H, s), 8.60 (1H, s), 8.34 (1H, s), 8.11 (1H, dd, J= 8.7 Hz, J = 1.5 Hz), 8.00 (1H, d, J = 2.7 Hz), 7.79 (1H, d, J = 8.7Hz), 7.72 (1H, dd, J = 8.7 Hz, J = 2.7 Hz), 7.48 (1H, dt, J = 6.0 Hz, J= 8.1 Hz), 7.36-7.31 (2H, m), 7.28 (1H, d, J = 9.0 Hz), 7.18 (1H, dt, J= 2.4 Hz, J = 8.4 Hz), 5.26 (2H, s), 4.28 (2H, t, J = 5.7 Hz), 2.63 (2H,t, J = 5.7 Hz), 2.23 (6H, s). V-10 —Cl

9.93 (1H, s) 8.63 (1H, s), 8.60 (1H, s), 8.33 (1H, s), 8.11 (1H, dd, J =8.7 Hz, J = 1.5 Hz), 8.01 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.7 Hz),7.72 (1H, dd, J = 2.7 Hz, J = 8.7 Hz), 7.47 (1H, dt, J = 5.7 Hz, J = 8.1Hz), 7.36-7.31 (2H, m), 7.28 (1H, d, J = 9.3 Hz), 7.18 (1H, dt, J = 8.7Hz, J = 2.7 Hz), 5.26 (2H, s), 4.25 (2H, t, J = 6.2 Hz), 2.79 (2H, brs),2.57 (4H, q, J = 6.6 Hz), 0.99 (6H, t, J = 7.1 Hz). V-11 —Cl

9.91 (1H, s), 8.61 (1H, d, J = 1.5 Hz), 8.60 (1H, s), 8.31 (1H, s), 8.12(1H, dd, J = 1.5 Hz, J = 8.7 Hz), 8.01 (1H, d, J = 2.4 Hz), 7.79 (1H, d,J = 8.7 Hz), 7.72 (1H, dd, J = 2.4 Hz, J = 8.7 Hz), 7.47 (1H, dt, J =5.7 Hz, J = 8.1 Hz), 7.36-7.31 (2H, m), 7.28 (1H, d, J = 9.3 Hz), 7.18(1H, dt, J = 8.7 Hz, J = 2.7 Hz), 5.26 (2H, s), 4.10 (2H, t, J = 6.9Hz), 3.01 (2H, quin, J = 6.3 Hz), 2.74 (2H, t, J = 6.9 Hz), 1.99 (12H,d, 6.3 Hz). V-12 —F

9.94 (1H, s), 8.64 (1H, s), 8.60 (1H, s), 8.34 (1H, s), 8.11 (1H, d, J =8.8 Hz), 7.88 (1H, d, J = 13.2 Hz), 7.79 (1H, d, J = 8.8 Hz), 7.56-7.44(2H, m), 7.36-7.24 (3H, m), 7.19 (1H, br t, J = 8.8 Hz), 5.18 (2H, s),4.32-4.27 (2H, m), 2.82-2.74 (2H, m), 2.55-2.48 (4H, m), 1.73-1.65 (4H,m). V-13 —OMe

9.84 (1H, s), 8.64 (1H, d, J = 1.5 Hz), 8.55 (1H, s), 8.34 (1H, s), 8.09(1H, dd, J = 1.5 Hz, J = 8.7 Hz), 7.77 (1H, d, J = 8.7 Hz), 7.49-7.36(3H, m), 7.33-7.26 (2H, m), 7.20-7.12 (1H, m), 7.05 (1H, d, J = 9.0 Hz),5.13 (2H, s), 4.28 (2H, t, J = 6.0 Hz), 3.82 (3H, s), 2.76 (2H, t, J =6.0 Hz), 2.54-2.46 (4H, m), 1.76-1.62 (4H, m).

TABLE 6 Compound No. R^(A) R^(B) ¹H-NMR(d₆-DMSO) V-23 Cl

9.96 (1H, s), 8.64 (1H, s), 8.60 (1H, s), 8.34 (1H, s), 8.11 (1H, dd, J= 1.2 Hz, J = 8.4 Hz), 8.01 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.7Hz), 7.72 (1H, dd, J = 2.4 Hz, J = 8.7 Hz), 7.48 (1H, dt, J = 6.0 Hz, J= 8.4 Hz), 7.36-7.30 (2H, m), 7.28 (1H, d, J = 9.0 Hz), 7.23-7.15 (1H,m), 5.27 (2H, s), 4.24 (2H, t, J = 5.7 Hz), 2.81 (2H, t, J = 5.7 Hz),2.33 (3H, s). V-24 Cl

9.95 (1H, s), 8.65 (1H, d, J = 1.2 Hz), 8.60 (1H, s), 8.35 (1H, s), 8.11(1H, dd, J = 1.5 Hz, J = 8.7 Hz), 8.01 (1H, d, J = 2.7 Hz), 7.79 (1H, d,J = 8.7 Hz), 7.73 (1H, dd, J = 2.7 Hz, J = 9.0 Hz), 7.47 (1H, dt, J =6.0 Hz, J = 8.1 Hz), 7.36-7.30 (2H, m), 7.28 (1H, d, J = 9.0 Hz),7.23-7.14 (1H, m), 5.26 (2H, s), 4.25 (2H, t, J = 5.7 Hz), 2.95 (2H, t,J = 5.7 Hz), 2.55-2.4 (1H, m), 1.9-1.8 (2H, m), 1.75-1.62 (2H, m),1.6-1.5 (1H, m), 1.3-0.97 (5H, m). V-25 OMe

9.86 (1H, s), 8.64 (1H, s), 8.56 (1H, s), 8.34 (1H, s), 8.10 (1H, d, J =8.4 Hz), 7.77 (1H, d, J = 8.7 Hz), 7.5-7.35 (3H, m), 7.34-7.26 (2H, m),7.21-7.13 (1H, m), 7.06 (1H, d, J = 8.7 Hz), 5.13 (2H, s), 4.23 (2H, t,J = 6.0 Hz), 3.82 (3H, s), 2.86 (2H, t, J = 6.0 Hz), 2.59 (2H, q, J =7.2 Hz), 1.02 (3H, t, J = 7.2 Hz). V-26 OMe

9.86 (1H, s), 8.64 (1H, s), 8.56 (1H, s), 8.33 (1H, s), 8.10 (1H, d, J =8.7 Hz), 7.77 (1H, d, J = 9.0 Hz), 7.50-7.35 (3H, m), 7.33-7.26 (2H, m),7.21-7.13 (1H, m), 7.05 (1H, d, J = 8.4 Hz), 5.13 (2H, s), 4.23 (2H, t,J = 5.7 Hz), 3.82 (3H, s), 2.81 (2H, d, J = 6.0 Hz), 2.33 (3H, s). V-27Ome

9.86 (1H, s), 8.64 (1H, s), 8.56 (1H, s), 8.34 (1H, s), 8.09 (1H, dd, J= 1.5 Hz, J = 8.7 Hz), 7.77 (1H, d, J = 8.7 Hz), 7.50-7.35 (3H, m),7.33-7.26 (2H, m), 7.21-7.13 (1H, m), 7.05 (1H, d, J = 8.7 Hz), 5.13(2H, s), 4.22 (2H, t, J = 5.7 Hz), 3.82 (3H, s), 2. 88 (2H, t, J = 5.7Hz), 2.45-2.35 (1H, m), 1.88-1.76 (2H, m), 1.72-1.62 (2H, m), 1.6-1.5(2H, m), 1.3-0.93 (4H, m). V-29 Cl

9.94 (1H, s), 8.65 (1H, trs), 8.60 (1H, s), 8.35 (1H, s), 8.11 (1H, dd,J = 8.7 Hz, J = 1.2 Hz), 8.00 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.7Hz), 7.72 (1H, dd, J = 9.0 Hz, J = 2.1 Hz), 7.51-7.44 (1H, m), 7.35-7.27(3H, m), 7.18 (1H, dt, J = 8.1 Hz, J = 1.5 Hz), 5.26 (2H, s), 4.12 (2H,d, J = 6.3 Hz), 3.53-3.44 (1H, m), 2.96-2.82 (2H, m), 1.94-1.64 (3H, m),1.53-1.41 (1H, m)

TABLE 7 Compound No. R^(A) R^(B) ¹H-NMR(d₆-DMSO) V-30 —Cl

9.95 (1H, s), 8.64 (1H, s), 8.59 (1H, s), 8.35 (1H, s), 8.11 (1H, d, J =8.7 Hz), 8.00 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.7 Hz), 7.71 (1H,dd, J = 8.4 Hz, J = 1.8 Hz), 7.44-7.51 (1H, m), 7.26-7.35 (3H, m),7.15-7.22 (1H, m), 5.26 (2H, s), 4.31 (2H, t, J = 5.7 Hz), 3.08-3.10(4H, m), 3.02-3.04 (4H, m), 2.91 (2H, t, J = 5.7 Hz) V-31 —Cl

9.95 (1H, s), 8.63 (1H, s), 8.60 (1H, s), 8.34 (1H, s), 8.11 (1H, d, J =9.3 Hz), 8.00 (1H, d, J = 2.7 Hz), 7.79 (1H, d, J = 8.7 Hz), 7.72 (1H,dd, J = 9.0 Hz, J = 2.4 Hz), 7.51-7.44 (1H, m), 7.35-7.27 (3H, m),7.22-7.15 (1H, m), 5.26 (2H, s), 4.23 (2H, t, J = 6.3 Hz), 3.09-3.07(4H, m), 2.92-2.90 (4H, m), 2.59 (2H, t, J = 6.9 Hz), 1.90-1.85 (2H, m)V-32 —Cl

9.94 (1H, s), 8.64 (1H, s), 8.59 (1H, s), 8.33 (1H, s), 8.10 (1H, d, J =8.7 Hz), 8.00 (1H, d, J = 2.7 Hz), 7.79 (1H, d, J = 8.7 Hz), 7.72 (1H,dd, J = 8.7 Hz, 2.4 Hz), 7.44-7.51 (1H, m), 7.26-7.35 (3H, m), 7.15-7.22(1H, m), 5.26 (2H, s), 4.22 (2H, t, J = 6.3 Hz), 2.49-2.51 (6H, m),1.78-1.83 (2H, m), 0.95 (6H, t, J = 7.2 Hz) V-33 —Cl

9.94 (1H, s), 8.61 (1H, s), 8.59 (1H, s), 8.31 (1H, s), 8.11 (1H, dd, J= 8.4 Hz, 1.5 Hz), 8.00 (1H, d, J = 2.7 Hz), 7.79 (1H, d, J = 8.7 Hz),7.71 (1H, dd, J = 9.3 Hz, 2.7 Hz), 7.44-7.51 (1H, m), 7.26-7.35 (3H, m),7.15-7.22 (1H, m), 5.26 (2H, s), 4.50-4.56 (1H, m), 3.57 (4H, t, J = 4.8Hz), 2.59-2.65 (2H, m), 2.46 (4H, m), 1.31 (3H, d, J = 6.0 Hz) V-34 —Cl

9.95 (1H, s), 8.65 (1H, s), 8.60 (1H, s), 8.34 (1H, s), 8.12 (1H, dd, J= 9.0 Hz, 1.8 Hz), 8.01 (1H, d, J = 2.7 Hz), 7.79 (1H, d, J = 8.7 Hz),7.72 (1H, dd, J = 8.7 Hz, J = 2.4 Hz), 7.44-7.52 (1H, m), 7.27-7.35 (3H,m), 7.16-7.22 (1H, m), 5.27 (2H, s), 4.25 (2H, t, J = 5.4 Hz), 3.25 (2H,t, J = 6.9 Hz), 3.02 (3H, s), 2.99 (2H, t, J = 6.9 Hz), 2.89 (2H, t, J =5.7 Hz) V-35 —Cl

9.95 (1H, s), 8.65 (1H, s), 8.60 (1H, s), 8.36 ( 1H, s), 8.12 (1H, dd, J= 8.7 Hz, 1.8 Hz), 8.01 (1H, d, J = 2.7 Hz), 7.80 (1H, d, J = 8.7 Hz),7.72 (1H, dd, J = 9.0 Hz, 2.4 Hz), 7.44-7.52 (1H, m), 7.27-7.35 (3H, m),7.16-7.22 (1H, m), 5.27 (2H, s), 4.04-4.09 (2H, m), 3.20-3.26 (2H, m),2.98-3.08 (6H, m), 1.06 (3H, d, J = 6.3 Hz)

TABLE 8 Compound No. R^(A) R^(B) ¹H-NMR(d₆-DMSO) V-36 —Cl

9.95 (1H, s), 8.63 (1H, s), 8.60 (1H, s), 8.32 (1H, s), 8.13 (1H, d, J =9.0 Hz), 8.00 (1H, d, J = 2.7 Hz), 7.80 (1H, d, J = 8.4 Hz), 7.72 (1H,dd, J = 9.3 Hz, 2.7 Hz), 7.44-7.52 (1H, m), 7.27-7.35 (3H, m), 7.16-7.22(1H, m), 5.27 (2H, s), 4.40-4.46 (1H, m), 3.27 (2H, t, J = 6.9 Hz),2.99-3.02 (5H, m), 2.74-2.90 (2H, m), 1.30 (3H, d, J = 6.6 Hz) V-37 —Cl

9.95 (1H, s), 8.64 (1H, s), 8.60 (1H, s), 8.34 (1H, s), 8.11 (1H, dd, J= 9.0 Hz, 1.2 Hz), 8.01 (1H, d, J = 2.7 Hz), 7.79 (1H, d, J = 8.7 Hz),7.72 (1H, dd, J = 8.7 Hz, 2.7 Hz), 7.44-7.51 (1H, m), 7.26-7.34 (3H, m),7.16-7.22 (1H, m), 5.26 (2H, s), 4.25 (2H, t, J = 6.3 Hz), 3.25 (2H, t,J = 7.2 Hz), 3.03 (3H, s), 2.98 (2H, t, J = 6.9 Hz), 2.70 (2H, t, J =6.9 Hz), 1.84-1.91 (2H, m) V-38 —Cl

9.96 (1H, s), 8.64 (1H, s), 8.60 (1H, s), 8.35 (1H, s), 8.11 (1H, dd, J= 8.7 Hz, 1.5 Hz), 8.01 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.7 Hz),7.73 (1H, dd, J = 9.0 Hz, 2.7 Hz), 7.44-7.52 (1H, m), 7.27-7.35 (3H, m),7.16-7.22 (1H, m), 5.27 (2H, s), 4.25 (2H, t, J = 5.4 Hz), 3.38-3.46(4H, m), 2.91 (2H, t, J = 5.7 Hz), 2.73 (2H, t, J = 5.4 Hz), 1.09 (3H,t, J = 6.9 Hz) V-39 —Cl

9.96 (1H, s), 8.63 (1H, brs), 8.60 (1H, s), 8.34 (1H, s), 8.11 (1H, dd,J = 8.7 H, J = 1.5 Hz), 8.00 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.7Hz), 7.72 (1H, dd, J = 9.0 Hz, J = 2.4 Hz), 7.52-7.44 (1H, m), 7.35-7.27(3H, m), 7.20 (1H, dt, J = 9.3 Hz, J = 2.7 Hz), 5.27 (2H, s), 4.37 (2H,t, J = 6.0 Hz), 3.51 (2H, t, J = 6.0 Hz) V-40 —Cl

9.95 (1H, s), 8.64 (1H, brs), 8.59 (1H, s), 8.40 (1H, s), 8.09 (1H, d, J= 6.6 Hz), 8.01 (1H, brs), 7.78 (1H, d, J = 6.3 Hz), 7.72 (1H, d, J =6.3 Hz), 7.50-7.45 (1H, m), 7.35-7.26 (3H, m), 7.19 (1H, t, J = 6.3 Hz),5.26 (2H, s), 5.09 (1H, m), 3.69 (2H, t-like, J = 5.1 Hz), 3.60 (2H,t-like, J = 5.1 Hz) V-41 —Cl

9.93 (1H, s), 8.62(1H, brs), 8.59 (1H, s), 8.30 (1H, s), 8.11 (1H, d, J= 6.3 Hz), 8.00 (1H, d, J = 1.5 Hz), 7.79 (1H, d, J = 6.6 Hz), 7.72 (1H,dd, J = 6.6 Hz, J = 1.8 Hz), 7.50-7.45 (1H, m), 7.35-7.27 (3H, m), 7.19(1H, t, J = 5.7 Hz), 5.26 (2H, s), 4.88 (1H, brs), 3.01-2.88 (3H, m),2.79-2.73 (1H, m), 1.99-1.85 (2H, m) V-42 —Cl

9.95 (1H, s), 8.63 (1H, brs), 8.60 (1H, s), 8.35 (1H, s), 8.11 (1H, dd,J = 8.7 Hz, J = 1.5 Hz), 8.01 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.7Hz), 7.72 (1H, dd, J = 9.3 Hz, J = 2.7 Hz), 7.52-7.44 (1H, m), 7.35-7.27(3H, m), 7.19 (1H, dt, J = 9.3 Hz, J = 2.7 Hz), 5.27 (2H, s), 4.29 (2H,t, J = 6.0 Hz), 2.69 (4H, t, J = 4.8 Hz), 2.63 (2H, t, J = 6.0 Hz), 2.39(4H, brs)

TABLE 9 Compound No. R^(A) R^(B) ¹H-NMR(d₆-DMSO) V-45 —Cl

9.93 (1H, s), 8.63 (1H, brs), 8.60 (1H, s), 8.33 (1H, s), 8.10 (1H, d, J= 6.6 Hz), 8.02 (1H, d, J = 1.5 Hz), 7.79 (1H, d, J = 6.6 Hz), 7.73 (1H,d, J = 6.9 Hz), 7.50-7.45 (1H, m), 7.35-7.27 (3H, m), 7.19 (2H, m), 7.08(1H, brs), 5.26 (2H, s), 4.20 (1H, dd, J = 8.1 Hz, J = 4.2 Hz), 4.13(1H, dd, J = 8.1 Hz, J = 4.2 Hz), 3.38 (1H, d, J = 12 Hz), 3.08-2.93(3H, m), 2.38 (1H, m), 199-1.89 (1H, m), 1.76-1.57 (3H, m) V-46 —Cl

9.93 (1H, s), 8.63 (1H, brs), 8.60 (1H, s), 8.34 (1H, s), 8.11 (1H, d, J= 6.6 Hz), 8.01 (1H, d, J = 2.1 Hz), 7.80 (1H, d, J = 6.6 Hz), 7.73 (1H,d, J = 8.1 Hz), 7.51-7.44 (1H, m), 7.35-7.27 (3H, m), 7.19 (1H, m), 5.27(2H, s), 4.38 (1H, brs), 4.19 (1H, dd, J = 8.1 Hz, J = 4.2 Hz), 4.03(1H, dd, J = 8.1 Hz, J = 4.2 Hz), 3.49 (2H, dd, J = 9.3Hz, J = 4.5 Hz),3.09-3.05 (1H, m), 2.95-2.90 (1H, m), 2.84-2.82 (1H, m), 2.47-2.40 (1H,m), 2.29-2.22 (1H, m), 1.91-1.85 (1H, m), 1.73-1.57 (3H, m) V-47 —Cl

9.94 (1H, s), 8.66 (1H, brs), 8.60 (1H, s), 8.43 (1H, s), 8.12 (1H, d, J= 6.6 Hz), 8.01 (1H, d, J = 1.2 Hz), 7.79 (1H, d, J = 6.9 Hz), 7.72 (1H,d, J = 6.6 Hz), 7.50-7.45 (1H, m), 7.35-7.27 (3H, m), 7.19 (1H, t, J =6.0 Hz), 5.27 (2H, s), 4.97 (1H, m), 3.74 (2H, s), 3.68 (2H, t-like, J =5.1 Hz), 3.37 (2H, t-like, J = 5.1 Hz) V-48 —Cl

9.95 (1H, s), 8.64 (1H, brs), 8.60 (1H, s), 8.39 (1H, s), 8.09 (1H, d, J= 6.6 Hz), 8.01 (1H, brs), 7.79 (1H, d, J = 6.3 Hz), 7.73 (1H, d, J =6.6 Hz), 7.50-7.45 (1H, m), 7.35-7.27 (3H, m), 7.19 (1H, t, J = 6.6 Hz),5.26 (2H, s), 4.92 (1H, m), 4.42 (1H, brs), 3.62 (2H, t, J = 5.4 Hz),3.14 (2H, t, J = 5.4 Hz), 2.54 (2H, t, J = 4.5 Hz) V-49 —Cl

9.94 (1H, s), 8.63 (1H, brs), 8.60 (1H, s), 8.32 (1H, s), 8.11 (1H, d, J= 6.6 Hz), 8.01 (1H, d, J = 1.8 Hz), 7.79 (1H, d, J = 6.6 Hz), 7.72 (1H,dd, J = 6.9 Hz, J = 1.8 Hz), 7.50-7.45 (1H, m), 7.35-7.27 (3H, m), 7.19(1H, t, J = 6.3 Hz), 5.26 (2H, s), 4.95 (1H, brs), 3.87 (2H, s),2.91-2.81 (3H, m), 2.57-2.51 (1H, m), 2.30-2.21 (1H, m), 2.00-1.91 (1H,m) V-50 —Cl

9.95 (1H, s), 8.62 (1H, brs), 8.59 (1H, s), 8.32 (1H, s), 8.10 (1H, d, J= 6.3 Hz), 8.00 (1H, brs), 7.79 (1H, d, J = 6.3 Hz), 7.72 (1H, d, J =6.3 Hz), 7.50-7.45 (1H, m), 7.35-7.27 (3H, m), 7.19 (1H, t, J = 6.0 Hz),5.26 (2H, s), 4.89 (1H, brs), 4.45 (1H, brs), 3.49 (3H, m), 2.82-2.75(3H, m), 2.41-2.39 (1H, m), 2.17 (1H, m), 1.86 (1H, brs)

TABLE 10 Compound No. R^(A) R^(B) ¹H-NMR(d₆-DMSO) V-51 —Cl

9.94 (1H, s), 8.64 (1H, s), 8.60 (1H, s), 8.33 (1H, s), 8.12 (1H, d, J =10.2 Hz), 8.01 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.7 Hz), 7.72 (1H,dd, J = 8.7 Hz, 2.4 Hz), 7.44-7.51 (1H, m), 7.26-7.34 (3H, m), 7.16-7.22(1H, m), 5.26 (2H, s), 4.29 (2H, t, J = 5.7 Hz), 3.27 (2H, t, J = 7.2Hz), 3.02 (3H, s), 2.84 (2H, t, J = 6.9 Hz), 2.75 (2H, t, J = 5.7 Hz),2.29 (3H, s) V-52 —Cl

9.94 (1H, s), 8.64 (1H, s), 8.59 (1H, s), 8.35 (1H, s), 8.10 (1H, dd, J= 8.7 Hz, 1.5 Hz), 8.00 (1H, d, J = 2.7 Hz), 7.78 (1H, d, J = 8.7 Hz),7.71 (1H, dd, J = 8.7 Hz, 2.4 Hz), 7.44-7.51 (1H, m), 7.26-7.35 (3H, m),7.15-7.21 (1H, m), 5.26 (2H, s), 4.32 (2H, t, J = 5.7 Hz), 3.42-3.43(4H, m), 2.71 (2H, t, J = 5.7 Hz), 2.41 (4H, t, J = 5.1 Hz), 1.98 (3H,s) V-53 —Cl

9.95 (1H, s), 8.63 (1H, s), 8.59 (1H, s), 8.35 (1H, s), 8.10 (1H, dd, J= 8.4 Hz, 1.2 Hz), 8.00 (d, 1H, J = 2.4 Hz), 7.79 (1H, d, J = 8.4 Hz),7.71 (1H, dd, J = 9.3 Hz, 2.4 Hz), 7.44-7.51 (1H, m), 7.26-7.34 (3H, m),7.15-7.22 (1H, m), 5.26 (2H, s), 4.32 (2H, t, J = 5.4 Hz), 3.43-3.45(4H, m), 2.70 (2H, t, J = 5.7 Hz), 2.41-2.46 (4H, m), 2.26 (2H, t, J =7.2 Hz), 1.43-1.56 (2H, m), 0.87 (3H, t, J = 7.5 Hz) V-54 —Cl

9.94 (1H, s), 8.63 (1H, s), 8.59 (1H, s), 8.35 (1H, s), 8.10 (1H, dd, J= 8.7 Hz, 1.5 Hz), 8.00 (1H, d, J = 2.4 Hz), 7.78 (1H, d, J = 8.7 Hz),7.71 (1H, dd, J = 9.0 Hz, 2.4 Hz), 7.44-7.51 (1H, m), 7.26-7.35 (3H, m),7.15-7.21 (1H, m), 5.26 (2H, s), 4.32 (2H, t, J = 5.7 Hz), 4.06 (3H, s),3.37-3.42 (4H, m), 3.27 (2H, s), 2.71 (2H, t, J = 5.7 Hz), 2.46 (4H, m)V-55 —Cl

9.94 (1H, s), 8.63 (1H, s), 8.59 (1H, s), 8.35 (1H, s), 8.10 (1H, dd, J= 8.7 Hz, 1.5 Hz), 8.00 (1H, d, J = 2.4 Hz), 7.79 (1H, d, J = 8.7 Hz),7.71 (1H, dd, J = 9.0 Hz, 2.4 Hz), 7.44-7.51 (1H, m), 7.26-7.35 (3H, m),7.15-7.21 (1H, m), 5.26 (2H, s), 4.32 (2H, t, J = 5.7 Hz), 3.53 (2H, t,J = 6.6 Hz), 3.43-3.47 (4H, m), 3.21 (3H, s), 2.71 (2H, t, J = 6.0 Hz),2.55 (2H, t, J = 6.6 Hz), 2.42-2.50 (4H, m) V-56 —Cl

9.94 (1H, s), 8.64 (1H, s), 8.59 (1H, s), 8.35 (1H, s), 8.10 (1H, dd, J= 8.7 Hz, 1.5 Hz), 8.00 (1H, d, J = 2.7 Hz), 7.79 (1H, d, J = 9.0 Hz),7.71 (1H, dd, J = 8.7 Hz, 2.4 Hz), 7.44-7.51 (1H, m), 7.26-7.35 (3H, m),7.15-7.22 (1H, m), 5.26 (2H, s), 4.61-4.66 (1H, m), 4.32 (2H, t, J = 5.7Hz), 3.68-3.80 (2H, m), 3.44-3.54 (4H, m), 2.71 (2H, 5.7 Hz), 2.44-2.50(4H, m), 1.95-2.04 (2H, m), 1.75-1.86 (2H, m)

TABLE 11 Compound No. R^(A) R^(B) ¹H-NMR(d₆-DMSO) V-57 —Cl

9.94 (1H, s), 8.64 (1H, s), 8.59 (1H, s), 8.35 (1H, s), 8.10 (1H, dd, J= 8.7 Hz, 1.2 Hz), 8.00 (1H, d, J = 2.7 Hz), 7.79 (1H, d, J = 8.7 Hz),7.71 (1H, dd, J = 9.0 Hz, 2.4 Hz), 7.44-7.51 (1H, m), 7.26-7.35 (3H, m),7.16-7.21 (1H, m), 5.26 (2H, s), 4.45 (2H, s), 4.32 (2H, t, J = 5.4 Hz),3.49-3.53 (4H, m), 3.09 (3H, s), 2.72 (2H, t, J = 5.7 Hz), 2.44-2.50(4H, m) V-58 —Cl

9.95 (1H, s), 8.64 (1H, s), 8.59 (1H, s), 8.35 (1H, s), 8.10 (1H, d, J =8.7 Hz), 8.00 (1H, d, J = 2.7 Hz), 7.78 (1H, d, J = 8.7 Hz), 7.69-7.73(1H, m), 7.44-7.51 (1H, m), 7.26-7.34 (3H, m), 7.16-7.22 (1H, m), 5.26(2H, s), 4.31 (2H, t, J = 5.7 Hz), 3.12 (4H, t, J = 5.1 Hz), 2.87 (3H,s), 2.75 (2H, t, J = 5.4 Hz), 2.58 (4H, t, J = 5.3 Hz)

Example 6

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(4-(N-(2-(methanesulfonyl)ethyl)-N-(2,2,2-trifluoroacetyl)amino)butyloxyimino)quinazoline(V-14)

In N,N-dimethylacetamide (1.5 ml) were dissolved4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(hydroxyimino)quinazoline(V-2, 84 mg) andN-(4-bromobutyl)-N-(2-methanesulfonylethyl)-2,2,2-trifluoroacetamide (71mg), and potassium carbonate (41 mg) was added, followed by stirring at60° C. for 13 hours with heating. Thereafter, the reaction mixture waspoured into 0.5M citric acid, followed by extraction with ethyl acetate.The organic layer was washed with water and aqueous sodium chloridesolution, and dried over magnesium sulfate. The crude product waspurified by silica gel chromatography (eluting with hexane:ethylacetate=1:4) to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(4-(N-(2-(methanesulfonyl)ethyl)-2,2,2-trifluoroacetamido)butyloxyimino)quinazoline(V-14, 41 mg) as a pale yellow solid.

¹H NMR (d₆-DMSO, δ): 9.94 (1H, s), 8.63 (1H, s), 8.59 (1H, s), 8.33 (1H,s), 8.10 (1H, dd, J=8.4 Hz, J=1.5 Hz), 8.00 (1H, d, J=2.4 Hz), 7.78 (1H,d, J=8.7 Hz), 7.71 (1H, dd, J=2.3 Hz, J=8.7 Hz), 7.47 (1H, dt, J-6.0 Hz,J=8.1 Hz), 7.36-7.31 (2H, m), 7.28 (1H, d, J=9.0 Hz), 7.18 (1H, dt,J=2.0 Hz, J=8.6 Hz), 5.26 (2H, s), 4.26-4.18 (2H, m), 3.79 (2H, t, J=7.1Hz), 3.60-3.44 (4H, m), 3.05 (3H, s), 1.78-1.66 (4H, m).

(Step 2) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(4-(2-(methanesulfonyl)ethylamino)butyloxyimino)quinazoline(V-15)

In 2.6 ml of a mixture (1:1) of tetrahydrofuran and methanol wasdissolved4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(4-(N-(2-(methanesulfonyl)ethyl)-2,2,2-trifluoroacetamido)butyloxyimino)quinazoline(V-14, 40 mg), and 86 μl of 1 mol/L aqueous sodium hydroxide solutionwas added, followed by stirring at room temperature for 14 hours, and at40° C. for 2 hour. After the reaction, the reaction mixture wasextracted with ethyl acetate, the organic layer was dried, and filtratewas concentrated. The concentrated residue was purified bychromatography (eluting with 0 to 3% methanol-contenting ethyl acetated)using an amino column, and the resulting pale yellow oil was powderedwith a mixture of hexane and ethyl acetate to obtain 4 (3-chloro4-(3-fluorobenzyloxy)phenylamino) 6 (4(2-(methanesulfonyl)ethylamino)butyloxyimino)quinazoline (V-15, 12 mg)as a pale yellow solid.

¹H NMR (d₆-DMSO, δ): 9.95 (1H, s), δ 63 (1H, s), 8.59 (1H, s), 8.33 (1H,s), 8.11 (1H, d, J=8.7 Hz), 8.01 (1H, d, J=2.4 Hz), 7.79 (1H, d, J=8.7Hz), 7.72 (1H, br d, J=9.0 Hz), 7.51-7.44 (1H, m), 7.36-7.31 (2H, m),7.28 (1H, d, J=9.0 Hz), 7.19 (1H, br t, J=9 Hz), 5.26 (2H, s), 4.20 (2H,t, J=6.6 Hz), 3.21 (2H, t, J=6.9 Hz), 2.91 (2H, t, J=6.6 Hz), 2.56 (2H,t, J=6.9 Hz), 1.73 (2H, quin, J=7 Hz), 1.51 (2H, quin, J=7 Hz).

Example 7

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-hydroxyethan-1-yl)quinazoline(VI-1)

In 30 mL of tetrahydrofuran was dissolved 620 mg of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-formylquinazoline(IV-1), the solution was cooled to 0° C. under the nitrogen atmosphere,and 4.9 mL of methylmagnesium bromide (0.93M tetrahydrofuran solution)was added dropwise. After the reaction at 0° C. for 1 hour under thenitrogen atmosphere, water and ethyl acetate were added to separate thelayers. The organic layer was washed sequentially with water and aqueoussaturated sodium chloride solution, and dried over magnesium sulfate.After concentration, the resulting crystal was washed with chloroform toobtain 330 mg of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-hydroxyethan-1-yl)quinazoline(VI-1).

¹H NMR (d₆-DMSO δ): 9.81 (1H, s), 8.55 (1H, s), 8.44 (1H, s), 8.03 (1H,J=2.4 Hz), 7.86 (1H, dd, J=8.7 Hz, J=1.2 Hz), 7.78-7.73 (2H, m),7.51-7.44 (1H, m), 7.35-7.25 (3H, m), 7.18 (1H, dt, J=8.4 Hz, J=2.4 Hz),5.44 (1H, d, J=3.9 Hz), 5.26 (2H, s), 4.93 (1H, m), 1.45 (3H, d, J=6.6Hz)

(Step 2) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(ethane-4-one)quinazoline(VII-1)

In 150 mL of tetrahydrofuran was dissolved 360 mg of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino-6-(1-hydroxyethan-1-yl)quinazoline(VI-1), and 3.7 g of manganese dioxide was added, followed by stirringat room temperature overnight. After the reaction, inorganic substanceswere filtered, and the filtrate was concentrated. The resulting crystalwas washed with chloroform to obtain 320 mg of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(ethane-4-one)quinazoline(VII-1).

¹H NMR (d₆-DMSO δ): 10.18 (1H, s), 9.16 (1H, d, J=1.5 Hz), 8.64 (1H, s),8.31 (1H, dd, J=8.4 Hz, J=2.4 Hz), 7.97 (1H, d, J=24 Hz), 7.83 (1H, d,J=8.7 Hz), 7.71 (1H, dd, J=8.7 Hz, J=2.4 Hz), 7.51-7.44 (1H, m),7.35-7.29 (3H, m), 7.19 (1H, dt, J=8.1 Hz, J=2.7 Hz), 5.27 (2H, s), 2.74(3H, s)

The following compounds were synthesized according to the same manner asthat of the above first step and second step.

TABLE 12 [Chemical formula 69] (VII)

Compound No. R^(B) ¹H-NMR(d₆-DMSO) VII-2 

10.17 (1H, s), 9.17 (1H, d, J = 1.5 Hz), 8.64 (1H, s), 8.32 (1H, dd, J =8.7 Hz, J = 1.5 Hz), 7.97 (1H, d, J = 2.7 Hz), 7.84 (1H, d, J = 8.7 Hz),7.72 (1H, dd, J = 8.7 Hz, J = 2.7 Hz), 7.52-7.44 (1H, m), 7.35-7.29 (3H,m), 7.20 (1H, dt, J = 8.7 Hz, J = 2.7 Hz), 5.28 (2H, s), 3.22 (2H, q, J= 7.2 Hz), 1.17 (3H, t, J = 7.2 Hz) VII-3 

(CDCl₃) 8.76 (1H, s), 8.65 (1H, brs), 8.29 (1H, d, J = 9.0 Hz), 7.97(1H, d, J = 8.4 Hz), 7.88 (1H, brs), 7.52 (1H, d, J = 9.0 Hz), 7.40-7.33(1H, m), 7.25-7.19 (3H, m), 7.05-6.97 (2H, m), 5.16 (2H, s), 3.72-3.63(1H, m), 1.28 (3H, d, J = 1.8 Hz), 1.26 (3H, d, J = 1.8 Hz) VII-4 

10.34 (1H, s), 9.23 (1H, s), 8.66 (1H, s), 8.44 (1H, dd, J = 9 Hz, J =1.5 Hz), 7.99 (1H, d, J = 2.7 Hz), 7.88 (1H, d, J = 8.7 Hz), 7.72 (1H,dd, J = 9 Hz, J = 2.4 Hz), 7.43-7.52 (1H, m), 7.14-7.36 (4H, m), 5.28(2H, s), 2.28 (3H, s) VII-5 

10.14 (1H, s), 8.98 (1H, s), 8.67 (1H, s), 8.11 (1H, dd, J = 8.7 Hz, J =0.9 Hz), 7.98-7.82 (4H, m), 7.78-7.58 (4H, m), 7.52-7.43 (1H, m),7.36-7.14 (4H, m), 5.26 (2H, s) VII-6 

10.50 (1H, s), 9.27 (1H, s), 8.67 (1H, s), 8.35 (1H, d, J = 9.3 Hz),7.99 (1H, d, J = 2.7 Hz), 7.88 (1H, brs), 7.70 (1H, d, J = 7.5 Hz),7.52-7.43 (1H, m), 7.36-7.14 (4H, m), 5.28 (2H, s) VII-8 

10.36 (1H, s), 9.26 (1H, s), 8.67 (1H, s), 8.44 (1H, dd, J = 8.7 Hz, J =1.8 Hz), 8.00 (1H, d, J = 2.4 Hz), 7.91 (1H, d, J = 8.7 Hz), 7.72 (1H,dd, J = 9.0 Hz, J = 2.4 Hz), 7.51-7.44 (1H, m), 7.35-7.28 (3H, m),7.22-7.15 (1H, m), 5.27 (2H, s), 4.55 (2H, s). VII-9 

10.4 (1H, s), 9.24 (1H, s), 8.67 (1H, s), 8.46 (1H, d, J = 8.7 Hz), 8.01(1H, d, J = 2.7 Hz), 7.90 (1H, d, J = 8.7 Hz), 7.70-7.80 (1H, m),7.44-7.54 (1H, m), 7.15-7.40 (4H, m), 5.27 (2H, s), 2.64 (2H, t, J = 6.9Hz), 1.63-1.75 (2H, m), 1.05 (3H, t, J = 7.5 Hz) VII-10

10.34 (1H, s), 9.24 (1H, s), 8.67 (1H, s), 8.42 (1H, d, J = 8.4 Hz),7.99 (1H, s), 7.88 (1H, d, J = 8.7 Hz), 7.73 (1H, d, J = 9.0 Hz),7.48-7.44 (1H, m), 7.34-7.27 (3H, m), 7.21-7.16 (1H, m), 5.27 (2H, s),4.76 (2H, s), 0.94 (9H, s), 0.16 (6H, s).

TABLE 13 [Chemical formula 70] (VII)

Compound No. R^(B) R^(C) ¹H-NMR(d₆-DMSO) VII-11

10 44 (1H, s), 9.24 (1H, s), 8.60 (1H, s), 8.43 (1H, dd, J = 2.4, 11.6Hz), 8.17 (2H, s), 7.87 (1H, d, J = 12.0 Hz), 7.78-7.67 (2H, m),7.41-7.34 (1H, m), 7.14-7.04 (3H, m), 5.72 (2H, s), 2.28 (3H, s) VII-12

10.47 (1H, s), 9.29 (1H, d, J = 1.8 Hz), 8.62 (1H, s), 8 43 (1H, dd, J =1.5 Hz, J = 9 0 Hz), 8.21-8.17 (2H, m), 7.89 (1H, d, J = 8.7 Hz),7.78-7.68 (2H, m), 7.41-7.33 (1H, m), 7.15-7.04 (3H, m), 5.71 (2H, s),4.55 (2H, s), 3.42 (3H, s). VII-13

10.44 (1H, s), 9.25 (1H, s), 8.73 (1H, s), 8.44 (1H, d, J = 8.8 Hz),8.16 (1H, s), 7.89 (1H, d, J = 8.4 Hz), 7.62 (1H, d, J = 8.4 Hz), 7.34(1H, dd, J = 8.4, 16.0 Hz), 6.95-6.86 (2H, m), 6.82-6.77 (1H, m), 5.15(2H, s), 2.27 (3H, s). VII-14

10.34 (1H, s), 9.22 (1H, s), 8.64-8.59 (2H, m), 8.43-8.41 (1H, m), 7.98(1H, s), 7.87-7 85 (2H, m), 7.71-7.68 (1H, m), 7.59-7.58 (1H, m),7.40-7.34 (1H, m), 7.29-7.27 (1H, m), 5.30 (2H, s). VII-15

9.21 (1H, s), 8.64-8.58 (2H, m), 8.45-8.39 (1H, m), 7.97 (1H, s),7.88-7.84 (1H, m), 7.71-7.66 (1H, m), 7.45-7.51 (1H, m), 7.27-7.23 (1H,m), 7.29-7 27 (1H, m), 5.30 (2H, s). VII-16

10.35 (1H, s), 9.24 (1H, s), 8.67 (1H, s), 8.60 (1H, d, J = 4.4 Hz),8.42 (1H, d, J = 8.8 Hz), 8.01 (1H, s), 7.91-7.87 (2H, m), 7.73-7.71(1H, m), 7 59 (1H, d, J = 8.0 Hz), 7.39-7.36 (1H, m), 7.29 (1H, d, J =8.8 Hz), 5.31 (2H, s), 4.55 (2H, s), 3.42 (3H, s).

TABLE 14 Compound No. R^(B) R^(C) ¹H-NMR(d₆-DMSO) VII-17

10.32 (1H, s), 8.85 (1H, s), 8.74 (1H, s), 8.20 (2H, d, J = 6.0 Hz),8.01-7.96 (4H, m), 7.87 (1H, d, J = 6.0 Hz), 7.68-7.64 (3H, m), 3.56(3H, s). VII-18

10.52 (1H, s), 9.14 (1H, s), 8.60 (1H, s), 8.31 (1H, d, J = 8.4 Hz),8.40 (2H, d, J = 8.4 Hz), 7.84-7.78 (5H, m), 7.52-7.43 (3H, m), 4.37(2H, s), 3.24 (3H, s). VII-19

10.44 (1H, s), 9.28 (1H, s), 8.70 (1H, s), 8.45 (1H, d, J = 8.8 Hz),7.92 (3H, t, J = 8.8 Hz), 7.46 (2H, d, J = 8.8 Hz), 7.37 (2H, t, J = 7.6Hz), 7.30-7.26 (3H, m), 4.24-4.20 (2H, m), 2.28 (3H, s).

(Step 3) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-(1-morpholino)ethoxyimino)ethyl)quinazoline(VIII-1)

In 6 mL (20:1) of a mixture of tetrahydrofuran and water were dissolved100 mg of Compound VII-1 and 78 mg of 2-(1 morpholino)ethoxyaminedihydrochloride, followed by stirring at room temperature overnight. Thereaction mixture was diluted with ethyl acetate, washed with aqueoussaturated sodium bicarbonate solution, and dried over magnesium sulfate.After concentration, the solid was washed with a mixture (2:1) of hexaneand ethyl acetate to obtain 72 mg of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-(1-morpholino)ethoxyimino)ethyl)quinazoline(VIII-1).

¹H NMR (d-DMSO, δ): 9.93 (1H, s), 8.62 (1H, brs), 8.58 (1H, s), 8.22(1H, d, J=6.6 Hz), 7.96 (1H, d, J=1.8 Hz), 7.76 (1H, d, J=6.6 Hz), 7.70(1H, dd, J=6.6 Hz, J=1.8 Hz), 7.51-7.45 (1H, m), 7.35-7.28 (3H, m), 7.19(1H, t, J=6.0 Hz), 5.27 (2H, s), 4.33 (2H, t, J=6.0 Hz), 3.59 (41H, t,J=4.5 Hz), 2.69 (2H, t, J=6.0 Hz), 2.47 (4H, t, J=45 Hz), 2.36 (3H, s)

Reference Example 1

As a method of obtaining a ketone derivative (VII), the following methodis exemplified in addition to the first step and the second step ofExample 7.

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylicacid methyl ester (X-1)

In a mixture of 200 ml of dimethylformamide and 200 ml of methanol weredissolved4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-iodoquinazolinehydrochloride (III-1, 20 g) and 1.29 g ofdichlorobis(triphenylphosphine)palladium, and 25.7 ml of triethylaminewas added. The interior of a reaction vessel was sufficiently replacedwith a carbon monoxide gas, followed by a reaction at 80° C. for 15hours under the carbon monoxide atmosphere. The reaction mixture wasfiltered with Celite, and the filtrate was cooled to 0° C. withstirring. A precipitate was filtered, washed with cold methanol, anddried to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazoline-6 carboxylicacid methyl ester (X-1, 13.5 g) as a colorless solid.

¹H NMR (d₆-DMSO, δ): 10.26 (1H, s), 9.25 (1H, d, J=1.5 Hz), 8.65 (1H,s), 8.31 (1H, dd, J=1.5 Hz, J=8.7 Hz), 8.02 (1H, d, J=2.7 Hz), 7.85 (1H,d, J=2.7 Hz), 7.77 (1H, dd, J=2.7 Hz, J=8.7 Hz), 7.49-7.44 (1H, m),7.35-7.27 (3H, m), 7.20-7.16 (1H, m), 5.27 (2H, s), 3.96 (3H, s).

(Step 2) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazoline-6-carboxylicacid methoxy methyl amide (XI-1)

In tetrahydrofuran (230 ml) was dissolved4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylicacid methyl ester (X-1, 11.6 g), N,O-dimethylhydroxylamine hydrochloride(7.8 g) was added, and 2 mol/L iPrMgCl tetrahydrofuran solution (79.8ml) was added dropwise over 30 minutes under ice cooling. Aftercompletion of addition, the mixture was stirred for 20 minutes under icecooling and, after completion of the reaction, 200 ml of aqueoussaturated ammonium chloride solution was added. After 100 ml of waterwas added to the mixture, the mixture was extracted with ethyl acetate,and the organic layer was dried over sodium sulfate. The filtrate wasconcentrated to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylicacid methoxy methyl amide (XI-1, 12.7 g) as a pale yellow solid.

¹H NMR (d₆-DMSO, δ): 10.01 (1H, s), 8.79 (1H, d, J=1.5 Hz), 8.64 (1H,s), 8.05 (1-H, d, J=2.7 Hz), 8.00 (1H, dd, J=1.5 Hz, J=8.7 Hz), 7.81(1H, d, J=−8.7 Hz), 7.76 (1H, dd, J=2.7 Hz, J=8.7 Hz), 7.52-7.44 (1H,m), 7.35-7.26 (3H, m), 7.22-7.16 (1H, m), 5.27 (2H, s), 3.57 (3H, s),3.34 (3H, s).

(Step 3) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-oxo-2-butyn-1-yl)quinazoline(VI-4)

To a solution of 4.22 ml of N,N-diisopropylamine in tetrahydrofuran (25ml) cooled to −78° C. was added dropwise 18.8 ml of 1.6 mol/L n-BuLihexane solution. After completion of addition, a temperature waselevated to 0° C., and the mixture was stirred at 0° C. for 20 minutes,and cooled again to −78° C. 1.33 ml of 2-bromo-1-propene intetrahydrofuran (25 ml) was added, and the mixture was stirred at −78°C. for 2 hours. To the mixture was added dropwise a solution of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylicacid methoxy methyl amide (XI-1, 2.33 g) in tetrahydrofuran (50 ml) and,after completion of addition, a temperature was elevated to 0° C.,followed by stirring for 3 hours. After completion of the reaction, thereaction mixture was poured into ice water, neutralized with 2 mol/Lhydrochloric acid, and extracted with ethyl acetate. The organic layerwas dried over sodium sulfate, the filtrate was concentrated, and theresulting crystalline residue was washed with methylene chloride toobtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-oxo-2-butyn-1-yl)quinazoline(VII-4, 1.71 g) as a yellow solid.

Reference Example 2

As other method of the third step of Reference Example 1, there isfollowing method.

(Step 3) Synthesis of4-(3-chlor-4-(3-fluorobenzyloxy)phenylamino)-6-(1-oxo-2-propyne-3-cyclopropyl-1-1-yl)quinazoline(VII-7)

To a solution of 0.16 ml of ethynylcyclopropane in tetrahydrofuran (3ml) cooled to −78° C. was added dropwise 1.25 ml of 1.54 mol/L n-BuLihexane solution. After completion of addition, the mixture was stirredat −78° C. for 1 hour. To the mixture was added dropwise a solution of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylicacid methoxy methyl amide (XI-1, 300 mg) in tetrahydrofuran (3 ml) and,after completion of addition, a temperature was elevated to 0° C., andthe mixture was stirred for 3 hours. After completion of the reaction,10 ml of water and ml of ethyl acetate were added to the reactionmixture to separate the layers. After the aqueous layer was re-extractedwith 10 ml of ethyl acetate two times, all organic layers were combined,and dried over sodium sulfate, and the filtrate was concentrated. Theresidue was purified by silica gel column chromatography to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-oxo-2-propyne-3-cyclopropyl-1-yl)quinazoline)(VII-7, 265 mg) as a yellow solid.

¹H NMR (d₆-DMSO, δ): 10.4 (1H, s), 9.21 (1H, s), 8.67 (1H, s), 8.41 (1H,d, J=8.7 Hz), 8.01 (1H, d, J=2.7 Hz), 7.88 (1H, d, J=8.7 Hz), 7.73 (1H,dd, J=8.7 Hz, J 3 Hz), 7.40-7.52 (1H, m), 7.15-7.4 (4H, m), 5.28 (2H,s), 1.77-1.87 (1H, m), 1.05-1.20 (3H, m).

Reference Example 3

As a method of obtaining an amide derivative (XI), there is followingmethod in addition to the first step and the second step of ReferenceExample 1.

(Step 1) Synthesis of 4-hydroxyquinazoline-6-carboxylic acid methylester (XII-1)

4-Hydroxy-6-iodoquinazoline (250 mg), a catalytic amount of palladium(II) acetate and 1,3-bis(diphenylphosphino)propane were dissolved inN,N-dimethylformamide (3.8 ml) and methanol (1.5 ml) and 1.5 ml oftriethylamine was added. After the interior of a reaction vessel wassufficiently replaced with a carbon monoxide gas, a reaction wasperformed at 80° C. for 20 hours under the carbon monoxide atmosphere.After completion of the reaction, the reaction mixture was poured into10% aqueous citric acid, followed by extraction with ethyl acetate. Theorganic layer was washed with water, and dried over sodium sulfate, andthe filtrate was concentrated. The resulting residue was purified bysilica gel column chromatography (eluting with ethyl acetate) to obtain4-hydroxyquinazoline-6-carboxylic acid methyl ester (XII-1, 157 mg) as abrown solid.

¹H NMR (d₆-DMSO, δ): 12.48 (1H, s), 8.63 (1H, s), δ 26 (1H, d, J=8.4Hz), 8.19 (1H, s), 7.73 (1H, d, J=8.4 Hz).

(Step 2) Synthesis of 4-hydroxyquinazoline-6-carboxylic acidmethoxymethylamide (XIII-1)

4-Hydroxyquinazoline-6-carboxylic acid methyl ester (XII-1, 4.0 g) wasdissolved in tetrahydrofuran (120 ml), N,O-dimethylhydroxylaminehydrochloride (5.7 g) was added, and 2 mol/L iPrMgCl tetrahydrofuransolution (59 ml) was added dropwise over 30 minutes. After completion ofaddition, the mixture was stirred for 30 minutes under ice cooling and,after completion of the reaction, 40 ml of 2 mol/L hydrochloric acid wasadded dropwise. The mixture was neutralized with aqueous saturatedsodium bicarbonate solution, and extracted with chloroform, and theorganic layer was washed with aqueous sodium chloride solution, anddried over sodium sulfate. After concentration, the crystalline residuewas purified by silica gel column chromatography (eluting ethyl acetate:methanol=9:1) to obtain 4-hydroxyquinazoline-6-carboxylic acidmethoxymethylamide (XIII-1, 2.9 g) as a white solid.

¹H NMR (d₆-DMSO, δ): 12.42 (1H, s), 8.36 (1H, s), 8.18 (1H, s), 8.02 (1,d, J=8.4 Hz), 7.73 (1H, d, J=8.4 Hz), 3.57 (3H, s), 3.32 (3H, s).

(Step 3) Synthesis of 4-chloroquinazoline-6-carboxylic acidmethoxymethylamide (XIV-1)

4-Hydroxyquinazoline-6-carboxylic acid methoxymethylamide (XIII-1, 2.9g) was suspended in toluene (57 ml), and 6.8 ml of triethylamine and 3.4ml of phosphorus oxychloride were added, followed by stirring at 130° C.for 30 minutes. After completion of the reaction, the reaction mixturewas cooled to room temperature, and 50 ml of aqueous saturated sodiumbicarbonate solution and ethyl acetate were added. Sodium bicarbonatewas added until the aqueous layer exhibited a pH 8, followed byextraction with ethyl acetate. The organic layer was washed with aqueoussaturated sodium bicarbonate solution, dried over sodium sulfate. Afterconcentration, the crystalline residue was washed with diethyl ether,and dried to obtain 4-chloroquinazoline-6-carboxylic acidmethoxymethylamide (XIV-1, 2.3 g) as a white solid.

¹H NMR (d₆-DMSO, δ): 8.75 (1H, s), 8.36 (1H, s), 8.11 (1H, dd, J=2.0 Hz,J=8.4 Hz), 7.87 (1H, d, J=8.4 Hz), 3.56 (3H, s), 3.32 (3H, s).

(Step 4) Synthesis of4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-quinazoline-6-carboxylicacid methoxymethylamide (XI-2)

4-Chloroquinazoline-6-carboxylic acid methoxymethylamide (XIV-1, 5.78 g)was dissolved in tetrahydrofuran (100 ml), and 5.39 g of3-chloro-4-(pyridin-2-ylmethoxy)aniline was added, followed by stirringat 60° C. for 1 hour. A precipitate was filtered, and washed withtetrahydrofuran to obtain4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-quinazoline-6-carboxylicacid methoxymethylamide (XI-2, 7.87 g) as a white solid. The filtratewas allowed to stand at room temperature, and the resulting precipitatewas collected by filtration, to newly obtain 2.21 g of XI-2.

¹H NMR (ds-DMSO, δ): 10.02 (1H, s), 8.79 (1H, s), 8.62-8.59 (2H, m),8.04 (1H, s), 8.00-7.98 (1H, m), 7.90-7.86 (1H, s), 7.80-7.78 (1H, m),7.75-7.73 (1H, m), 7.59-7.57 (1H, m), 7.37-7.35 (1H, m), 7.28-7.26 (1H,m), 5.29 (2H, s), 3.57 (3H, s).

Reference Example 4

As other method of the fourth step of Reference Example 3, there isfollowing method.

(Step 4) Synthesis of4-(4-benzenesulfonylphenylamino)-quinazoline-6-carboxylic acidmethoxymethylamide (XI-3)

4-Chloroquinazoline-6-carboxylic acid methoxymethylamide (XIV-1, 550rag), 611 mg of 4-benzenesulfonylphenylamine, 49 mg of palladium (II)acetate, 190 mg of Xant phos and 997 mg of cesium carbonate were addedto 1,4-dioxane (30 ml), and the interior of a reaction vessel wasreplaced with a nitrogen gas, followed by stirring at 100° C. for 2.5hours. The reaction mixture was filtrated with Celite, and water wasadded to the filtrate, followed by extraction with ethyl acetate. Theorganic layer was washed with aqueous saturated sodium chloridesolution, and dried over sodium sulfate. The filtrated was concentrated,and the residue was purified by silica gel column chromatography(eluting with ethyl acetate:methanol=95:5) to obtain4-(4-benzenesulfonylphenylamino)-quinazoline-6-carboxylic acidmethoxymethylamide (XI-3, 651 tag) as a pale yellow solid.

¹H NMR (d₆-DMSO, δ): 10.66 (1H, s), 9.29 (1H, s), 8.80 (1H, s), 8.48(1H, d, J=7.7 Hz), 8.16 (2H, d, J=7.7 Hz), 7.99-7.94 (5H, m), 7.80-7.61(3H, m), 2.27 (3H, s).

Reference Example 5

As a method of obtaining an amide derivative (XI), there is further thefollowing method in addition to the first step and the second step ofReference Example 1, and Reference Example 3.

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylicacid methoxymethylamide (XI-1)

4 (3 Chloro-4-((3-fluorobenzyloxy)phenylamino)-6-iodoquinazolinehydrochloride (III-1, 500 mg), 32 mg ofdichlorobis(triphenylphosphine)palladium, and 191 mg ofN-hydroxysuccinimide were dissolved in 10 ml of dimethylformamide, and360 td of triethylamide was added. The interior of a reaction vessel wassufficiently replaced with a carbon monoxide gas, followed by a reactionat 80° C. for 3 hours under the carbon monoxide atmosphere. To ⅕ of thereaction mixture was added 0.3 ml of a 40% N,O-dimethylhydroxylamineaqueous solution, followed by stirring at room temperature overnight.After completion of the reaction, water was added to the reactionmixture, followed by extraction with ethyl acetate. The organic layerwas washed with water and aqueous saturated sodium chloride solution inthis order, and dried over sodium sulfate. The concentrated residue ofthe filtrate was purified by silica gel column chromatography (elutingwith ethyl acetate) to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylicacid methoxymethylamide (XI-1, 74 mg) as a pale yellow solid.

Example 8

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-((S)-morpholin-2-ylmethoxyimino)-2-butyn-1-yl)quinazolinedihydrochloride (VIII-32)

To a suspension of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-oxo-2-butyn-1-yl)quinazoline(VII-4, 786 mg) and 614 mg of(S)-2-aminooxymethyl-morpholine-4-carboxylic acid tert-butyl ester in 31ml of 1,4-dioxane was added 2.21 ml of 2 mol/L methanesulfonic acidaqueous solution, followed by stirring at 80° C. for 22 hours. And, 1.32ml of 2 mol/L methanesulfonic acid aqueous solution was additionallyadded, followed by further stirring for 5.5 hours. After completion ofthe reaction, the reaction mixture was poured into aqueous sodiumbicarbonate solution, followed by extraction with ethyl acetate. Afteran aqueous layer was re-extracted with ethyl acetate, all organic layerswere combined, washed with water, and dried over anhydrous magnesiumsulfate. After the filtrate was concentrated, the residue was purifiedby silica gel column chromatography (eluting with chloroform:methanol=9:1) to obtain a yellow oil. This oil was dissolved in 50 ml ofethyl acetate, and filtered, and 0.95 ml of 4 mol/L hydrochloricacid-ethyl acetate solution was added with stirring, followed bystirring at room temperature for 1 hour. A precipitate was filtered, andwashed with ethyl acetate and hexane in this order. A substancecollected by filtration was recrystallized with methanol-ethyl acetateto obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-((S)-morpholin-2-ylmethoxyimino)-2-butyn-1-yl)quinazolinedihydrochloride (VIII-32, 839 mg) as a yellow crystal.

¹H NMR (d₆-DMSO, δ): 11.69 (1H, bs), 9.49-9.37 (2H, m), 9.05 (1H, s),8.88 (1H, s), 8.38 (1H, dd, J=1.5 Hz, J=8.7 Hz), 7.96 (1H, d, J=8.7 Hz),7.89 (1H, d, J=2.7 Hz), 7.64 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.52-7.45(1H, m), 7.36-7.30 (3H, m), 7.23-7.16 (1H, m), 5.31 (2H, s), 4.36-4.34(1H, m), 4.25-4.22 (1H, m), 4.04-3.98 (1H, m), 3.84-3.77 (1H, m),3.04-2.85 (3H, m), 2.28 (3H, s).

Example 9

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-hydroxyethoxyimino)-2-butyn-1-yl)quinazoline(VII-33)

4-(3-Cloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-oxo-2-butyn-1-yl)quinazoline(VII-4, 10 g) was dissolved in 300 ml of 1,4-dioxane, 1.5 equivalent of2-(acetoxy)ethoxyamine was added, and 28 ml of 2 mol/L aqueousmethanesulfonic acid solution was added, followed by stirring at 60° C.for 17 hours. The reaction mixture was poured into aqueous saturatedsodium bicarbonate solution, and the mixture was extracted with ethylacetate. The organic layer was washed with water, and dried over sodiumsulfate. The residue obtained by concentrating the filtrate wasrecrystallized from hydrous ethanol-water, filtered, and dried to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-hydroxyethoxyimino)-2-butyn-1-yl)quinazoline(VIII-33, 7.6 g) as a colorless solid.

¹H NMR (d₆-DMSO, δ): 10.07 (1H, s), 8.74 (1H, s), 8.58 (1H, s), 8.22(1H, d, J=8.8 Hz), 7.96 (1H, d, J=2.4 Hz), 7.80 (1H, d, J=8.8 Hz), 7.69(1H, dd, J=2.4 Hz, J=8.8 Hz), 7.50-7.45 (1H, m), 7.35-7.24 (3H, m),7.20-7.16 (1H, m), 5.27 (2H, s), 4.79 (1H, t, J=5.6 Hz), 4.29 (2H, t,J=5.6 Hz), 3.75 (2H, dd, J=5.2 Hz, J=10.4 Hz), 2.26 (3H, s).

(Step 2) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-sulfonyloxyethoxyimino)-2-butyn-1-yl)quinazoline(VIII-34)

4-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-hydroxyethoxyimino)-2-butyn-1-yl)quinazoline(VIII-33, 7.6 g) was dissolved in 150 ml of tetrahydrofuran, and 4.19 mlof triethylamine and 2.33 ml of methanesulfonyl chloride were added,followed by stirring for 3.5 hours. After completion of the reaction,the reaction mixture was poured into water, and aqueous saturated sodiumbicarbonate solution was added, followed by extraction with ethylacetate. The organic layer was dried over sodium sulfate, and thefiltrate was concentrated. Ethyl acetate was added to the concentratedresidue, this was allowed to stand at room temperature, a crystal wasprecipitated, and diluted with hexane, and the crystal was collected byfiltration to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-sulfonyloxyethoxyimino)-butyn-1-yl)quinazoline(VIII-34, 7.66 g) as a pale yellow crystal. ¹H NMR (d₆-DMSO, δ): 10.07(1H, s), 8.77 (1H, s), 8.60 (1H, s), 8.24 (1H, d, J=8.8 Hz), 7.97 (1H,d, J=2.4 Hz), 7.81 (1H, d, J=8.8 Hz), 7.69 (1H, dd, J=2.4 Hz, J=8.8 Hz),7.51-7.45 (1H, m), 7.35-7.27 (3H, m), 7.21-7.17 (1H, m), 5.27 (2H, s),4.58 (2H, t, J=4.8 Hz), 4.54 (2H, t, J=4.8 Hz), 3.24 (3H, s), 2.27 (3H,s).

4-(3Chloro-4-(pyridin-2-ylmethoxy)phenylamino)-6-(1-(2-sulfonyloxyethoxyimino)-2-butyn-1-yl)quinazoline(VIII-36)

The compound was synthesized according to the same manner as that of thefirst step and the second step.

¹H NMR (d₆-DMSO, δ): 10.09 (1H, s), 8.77 (1H, s), 8.61 (1H, s), 8.59(1H, s), 8.24 (1H, d, J=8.1 Hz), 7.97 (1H, d, J=2.4 Hz), 7.89 (1H, t,J=7.5 Hz), 7.81 (1H, d, J=9.0 Hz), 7.68 (1H, dd, J=2.4 Hz, J=9.0 Hz),7.59 (1H, d, J=8.1 Hz), 7.40-7.35 (1H, m), 7.29 (1H, d, J=9.0 Hz), 5.31(2H, s), 4.57 (2H, bs), 4.55 (2H, bs), 3.24 (3H, s). 2.27 (3H, s).

4-(1-(3-Fluorobenzyl)-1H-indazol-5-ylamino)6-(1-(2-sulfonyloxyethoxyimino)-2-butyn-1-yl)quinazoline (VIII-37)

The compound was synthesized according to the same manner as that of thefirst step and the second step.

¹H NMR (d₆-DMSO, δ): 10.20 (1H, s), 8.81 (1H, s), 8.53 (1H, s), 8.24(1H, d, J=8.7 Hz), 8.17 (1H, s), 8.13 (1H, s), 7.80 (1H, d, J=8.7 Hz),7.75 (1H, d, J=8.7 Hz), 7.67 (1H, d, J=9.3 Hz), 7.41-7.36 (1H, m),7.14-7.04 (3H, m), 5.72 (2H, s), 4.58 (2H, t, J=5.4 Hz), 4.54 (2H, t.J=5.4 Hz), 3.24 (3H, s), 2.26 (3H, s).

(Step 3) Synthesis of4-(3-chloro-4-3-fluorobenzyloxy)phenylamino)-6-(1-2-ethylaminoethoxyimino)-2-butyn-1-yl)quinazoline(VIII-35)

4-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(1-(2-sulfonyloxyethoxyimino)-2-butyn-1-yl)quinazoline(VIII-34, 10 mg) was dissolved in 3 ml of N,N-dimethylformamide, and160.1 g of 70% aqueous ethylamine solution was added, followed bystirring at 60° C. for 14 hours. Water was added to the reactionmixture, followed by extraction with ethyl acetate. The organic layerwas dried over magnesium sulfate, and the concentrated residue of thefiltrate was purified by chromatography (eluting with ethyl acetate)using an amino column to obtain4-(3-chloro-4-3-fluorobenzyloxy)phenylamino)-6-(1-(2-ethylaminoethoxyimino)-2-butyn-1-yl)quinazoline(VIII-35, 53 mg) as a colorless solid.

¹H NMR (d₆-DMSO, δ): 10.08 (1H, s), 8.74 (1H, s), 8.50 (1H, s), 8.21(1H, d, J=8.4 Hz), 7.96 (1H, s), 7.80 (1H, d, J=8.8 Hz), 7.69 (1H, d,J=8.0 Hz), 7.51-7.45 (1H, m), 7.35-7.27 (3H, m), 7.21-7.16 (1H, m), 5.27(2H, s), 4.31 (2H, t, J=5.6 Hz), 2.80 (2H, t, J=6.0 Hz), 2.61 (2H, q,J=7.2 Hz), 2.26 (3H, s), 1.02 (3H, t, J=7.6 Hz).

In amination of the third step, amine which is commercially available oramine which can be synthesized according to the method described in J.Syn. Org. Chem., Jpn., 2001, 59:779-789, Tetrahedron Lett., 1995,36:6373-6374, Synlett, 1999:1301-1303, Tetrahedron, 2002, 58:6267-6276or a salt thereof can be used.

Example 10

(Step 1) Synthesis of4-(3-Chloro-4-hydroxyphenylamino)-6-iodoquinazoline (III-4)

According to the same manner as that of the first step of Example 1 andusing 20.3 g of 4-chloro-6-iodoquinazoline and 10 g of3-chloro-4-hydroxyaniline,4-(3-chloro-4-hydroxyphenylamino)-6-iodoquinazoline hydrochloride(III-4, 26.6 g) was obtained as a yellow solid.

¹H NMR (d₆-DMSO, δ): 11.4 (1H, s), 10.5 (1H, s), 9.21 (1H, s), 8.93 (1H,s). 8.35 (1H, d, J=8.4 Hz), 7.79 (1H, s), 7.69 (1H, d, J=9.0 Hz), 7.48(1H, d, J=9.0 Hz), 7.10 (1H, d, J=8.4 Hz).

(Step 2) Synthesis of4-(3-chloro-4-triisopropylsilyloxyphenylamino)-6-iodoquinazoline (III-5)

4-(3-Chloro-4-3-fluorobenzyloxy)phenylamino)-6-iodoquinazolinehydrochloride (II-4, 20 g), 13.3 g of triisopropylsilane chloride, and12.6 g of imidazole were dissolved in 200 ml of N,N-dimethylformamide,followed by stirring at room temperature for 4 hour. After completion ofthe reaction. 200 ml of aqueous saturated sodium bicarbonate solutionand 200 ml of ethyl acetate were added to separate the layers. Theaqueous layer was re-extracted with 200 ml of ethyl acetate two times,and all organic layer were combined, washed with water and aqueoussaturated sodium chloride solution in this order, and dried overanhydrous magnesium sulfate. The filtrate was concentrated, and theresidue was washed with a hexane-ethyl acetate (2:1) to obtain4-(3-chloro-4-triisopropylsilyloxyphenylamino)-6-iodoquinazoline (III-5,25.3 g) as a colorless solid.

¹H NMR (d₆-DMSO, δ): 9.8 (1H, s), 8.96 (1H, s), 8.62 (1H, s), 8.12 (1H,d, J=8.7 Hz). 8.02 (1H, d, J=2.7 Hz), 7.70 (1H, dd, J=8.7 Hz, J=2.7 Hz),7.56 (1H, d, J=8.7 Hz), 7.04 (1H, d, J=8.7 Hz), 1.25-1.40 (3H, m), 1.1(18H, d, J=7.2 Hz).

(Step 3) Synthesis of4-(3-chloro-4-triisopropylsilyloxyphenylamino)-quinazoline-6-carboxylicacid methyl ester (X-2)

From 4-(3-chloro-4-triisopropylsilyloxyphenylamino)-6-iodoquinazoline(III-5, 21.8 g), 4-(3-chloro4-triisopropylsilyloxyphenylamino)-quinazoline-6-carboxylic acid methylester (X-2, 20.4 g) was obtained as a yellow solid according to the samemanner as that of the first step of Reference Example 1.

¹H NMR (d₆-DMSO, δ): 10.2 (1H, s), 9.26 (1H, s), 8.66 (1H, s), 8.30 (1H,d, J=8.7 Hz), 8.01 (1H, d, J=2.4 Hz). 7.84 (1H, d, J=8.7 Hz), 7.71 (1H,dd, J=9 Hz, J=2.1 Hz), 7.04 (1H, d, J=8.7 Hz), 3.96 (3H, s), 1.29-1.41(3H, m), 1.11 (18H, d, J=7.2 Hz).

(Step 4) Synthesis of4-(3-chloro-4-triisopropylsilyloxyphenylamino)-quinazoline-6-carboxy icacid methoxymethylamide (XI-4)

From4-(3-chloro-4-triisopropylsilyloxyphenylamino)-quinazoline-6-carboxylicacid methyl ester (X-2, 10 g),4-(3-chloro-4-triisopropylsilyloxyphenylamino)-quinazoline-6-carboxylicacid methoxymethylamide (XI-4, 4.1 g) was obtained as a colorless solidaccording to the same manner as that of the second step of ReferenceExample 1.

¹H NMR (d₆-DMSO, δ): 10.0 (1H, s), 8.80 (1H, s), 8.65 (1H, s), 7.97-8.08(2H, m), 7.81 (1H, d, J=8.7 Hz), 7.70-7.75 (1H, m), 7.04 (1H, d, J=9.0Hz), 3.58 (3H, s), 3.35 (3H, s), 1.29-1.41 (3H, m), 1.11 (18H, d, J=7.5Hz).

(Step 5) Synthesis of4-(3-chloro-4-triisopropylsilyloxyphenylamino)-6-(1-oxo-2-butyn-1-yl)quinazoline(VII-20)

From4-(3-chloro-4-triisopropylsilyloxyphenylamino)-quinazoline-6-carboxylicacid methoxymethylamide (XI-4, 4.1 g),4-(3-chloro-4-triisopropylsilyloxyphenylamino)-6-(1-oxo-2-butyn-1-yl)quinazoline(VII-20, 1.3 g) was obtained as a yellow oil according to the samemanner as that of the third step of Reference Example 1.

¹H NMR (d₆-DMSO, δ): 10.3 (1H, s), 9.24 (1H, s), 8.67 (1H, s), 8.45 (H,d, J=8.7 Hz), 7.99 (1H, s), 7.88 (1H, s, J=8.7 Hz). 7.68 (1H, d, J=9.0Hz), 7.06 (1H, d, J=9.0 Hz), 2.28 (3H, s), 1.29-1.41 (3H, m), 1.11(0.8H, d, J=6.9 Hz).

(Step 6) Synthesis of4-(3-chloro-4-triisopropylsilyloxyphenylamino)-6-1-(1-(N-(tert-butoxycarbonyl)-N-methylaminoethoxyimino)-2-butyn-1-yl)quinazoline(VIII-201)

From4-(3-chloro-4-triisopropylsilyloxyphenylamino)-6-(1-oxo-2-butyn-1-yl)quinazoline(VII-20, 1.3 g),4-(3-chloro-4-triisopropylsilyloxyphenylamino)-6-(2-((N-(tert-butoxycarbonyl)-N-methylaminoethoxyimino)-2-butyn-1-yl)quinazoline(VII-201, 1.1 g) was obtained as a yellow solid according to the samemanner as that of the second step of Example 2.

ESI-MS (M/Z): (M+)=666.71, (M+H)=667.73

(Step 7) Synthesis of4-(3-chloro-4-hydroxyphenylamino)-6-(1-(2-(N-(tert-butoxycarbonyl)-N-methylaminoethoxyimino)-2 butyn-1-yl)quinazoline (VIII-202)

4-(3-Chloro-4-triisopropylsilyloxyphenylamino)-6-(1-(2-(N-(tert-butoxycarbonyl)-N-methylaminoethoxyimino)-2-butyn-1-yl)quinazoline(VIII-201, 1.1 g) was dissolved in 20 ml of tetrahydrofuran, and 6.7 mlof 1 mol/L solution of tetrabutylammonium fluoride in tetrahydrofuranwas added, followed by stirring at room temperature for 30 minutes.After completion of the reaction, ml of water and 10 ml of ethyl acetatewere added to separate the layers. The aqueous layer was re-extractedwith 10 ml of ethyl acetate two times, and all organic layers werecombined, washed with water and aqueous saturated sodium chloridesolution, and dried over anhydrous magnesium sulfate. The filtrate wasconcentrated, and the residue was washed with a hexane-ethyl acetate(1:1) to obtain4-(3-chloro-4-hydroxyphenylamino)-6-(1-(2-(N-(tert-butoxycarbonyl)-N-methylaminoethoxyimino)-2-butyn-1-yl)quinazoline(VIII-202, 0.7 g) as a yellow solid.

¹H NMR (d₆-DMSO, δ): 9.96 (1H, s), 8.73 (1H, s), 8.55 (1H, s), 8.21 (1H,d, J=8.7 Hz), 7.75-7.86 (2H, m), 7.50 (1H, d, J=7.8 Hz), 7.00 (1H, d,J=8.7 Hz), 4.36 (2H, bs), 3-56 (2H, bs), 2.86 (3H, bs), 2.25 (3H, bs),1.36 (9-H, s).

(Step 8) Synthesis of4-(3-chloro-4-(pyridin-3-ylmethoxy)phenylamino)-6-(1-(2-(N-(tert-butoxycarbonyl)-N-methylaminoethoxyimino)-2-butyn-1-yl)quinazoline(VIII-203)

4-(3-Chloro-4-hydroxyphenylamino)-6-(1(2-(N-(tert-butoxycarbonyl)-N-methylaminoethoxyimino)-2-butyn-1-yl)quinazoline(VIII-202, 70 mg), 87 mg of 3-bromomethylpyridine hydrobromide, and 223mg of cesium carbonate were dissolved in 1.1 ml of aN,N-dimethylformamide-water (10.1), followed by stirring at roomtemperature for 3 hours. After completion of the reaction, 5 ml of waterand 5 ml of ethyl acetate were added to separate the layers. The aqueouslayer was re-extracted with 5 ml of ethyl acetate two times, and allorganic layers were combined, washed with water and aqueous saturatedsodium chloride solution in this order, and dried over anhydrousmagnesium sulfate. The filtrate was concentrated, and the residue waspurified by silica gel column chromatography (eluting with hexane:ethylacetate=1:1) to obtain 4-(3-chloro 4-(pyridin-3ylmethoxy)phenylamino)-6-(1-(2-(N-(tert-butoxycarbonyl)-N-methylaminoethoxyimino)-2-butyn-1-yl)quinazoline(VIII-203, 70 mg) as a yellow oil.

¹H NMR (d₆-DMSO, 8): 10.0 (1H, bs), 8.74 (1H, bs), 8.72 (1H, bs), 8.60(1H, s), 8.57 (1H, d, J=4.4 Hz), 8.23 (1H, d, J=8.8 Hz), 7.97 (1H, bs),7.91 (1H, d, J=8.0 Hz), 7.80 (1H, d, J=8.8 Hz), 7.72 (1H, d, J=8.8 Hz),7.46 (1H, dd, J=7.6 Hz, J=4.4 Hz), 7.33 (1H, d, J=8.8 Hz), 5.29 (2H, s),4.37 (2H, bs), 3.56 (2H, bs), 2.86 (3H, bs), 2.25 (3H, bs), 1.36 (9H,s).

(Step 9) Synthesis of 4-(3-chloro-4-(pyridin-3-ylmethoxy)phenylamino)6-(1-(2-N-methylaminoethoxyimino)-2-butyn-1-yl)quinazoline (VIII-204)

Starting from4-(3-chloro-4-(pyridin-3-ylmethoxy)phenylamino)-6-(1-(2-(N-(tert-butoxycarbonyl)-N-methylaminoethoxyimino)-2-butyn-1-yl)quinazoline(VIII-203, 70 mg), and according to the same manner as that of thesecond step of Example 2, the reaction was performed, and purificationwas performed by recrystallization from hexane-ethyl acetate to obtain4-(3-chloro-4-(pyrindin-3-ylmethoxy)phenylamino)-6-(1-(2-N-methylaminoethoxyimino)-2-butyn-1-yl)quinazoline(VIII-204, 7 mg) as a yellow solid. 10.3 (1H, s), 8.84 (1H, s), 8.72(1H, s), 8.42-8.65 (2H, m), 8.26 (1H, d. J=7.6 Hz), 7.98 (1H, s), 7.91(1H, brs), 7.81 (1H, bs), 7.71 (1H, brs), 7.47 (1H, brs), 7.34 (1H, d,J=8.0 Hz), 5.30 (2H, s), 4.53 (2H, brs), 3.38 (2H, brs), 2.68 (3H, s),2.26 (3H, s).

According to the same manner as that of Examples 7 to 10, the followingcompound was synthesized.

TABLE 15 [Chemical formula 81] (VIII)

Compound R^(B) ¹H-NMR(d₆-DMSO) VIII-2

9.92 (1H, s), 8.65 (1H, brs), 8.62 (1H, s), 8.22 (1H, d, J = 6 6 Hz),7.96 (1H, d, J = 2.1 Hz), 7.76 (1H, d, J = 6.6 Hz), 7.70 (1H, dd, J =6.6 Hz, J = 1.8 Hz), 7.53- 7.45 (1H, m), 7.35-7.28 (3H, m), 7.18 (1H, t,J = 5.7 Hz), 5.27 (2H, s), 4.30 (2H, t, J = 4.5 Hz), 2.64 (2H, t, J =4.5 Hz), 2.43 (4H, brs), 2.35 (3H, s), 1.53-1.47 (4H, m), 1.40-1.36 (2H,m). VIII-3

9.92 (1H, 8), 8.62 (1H, brs), 8.58 (1H, s), 8.23 (1H, d, J = 6.6 Hz),7.96 (1H, d, J = 1.8 Hz), 7.76 (1H, d, J = 6.6 Hz), 7.70 (1H, d, J = 6.9Hz), 7.50-7.45 (1H, m), 7.35-7.28 (3H, m), 7.18 (1H, t, J = 6.9 Hz),5.27 (2H, s), 4.26 (2H, t, J = 4.5 Hz), 2.77 (2H, t, J = 4.5 Hz), 2.55(4H, q, J = 5.4 Hz), 2.36 (3H, s), 0.96 (2H, t, J = 5.4 Hz) VIII-4

(mono · HCl salt) 11.4 (1H, brs), 10.82 (1H, brs), 9.07 (1H, s), 8.82(1H, s), 8.40 (1H, d, J = 10.2 Hz), 7.94 (1H, d, J = 2.7 Hz), 7.88 (1H,d, J = 9.0 Hz), 7.70 (1H, dd, J = 8.7 Hz, 2.7 Hz), 7.45-7.52 (1H, m),7.31-7.36 (3H, m), 7.17-7.23 (1H, m), 5.30 (2H, s), 4.94 (1H, m), 3.85(4H, m), 3.36-3.60 (6H, m), 2.44 (3H, s), 1.38 (3H, d, J = 6.3 Hz)VIII-5

9.93 (1H, s), 8.62 (1H, brs), 8.58 (1H, s), 8.22 (1H, d, J = 6.6 Hz),7.96 (1H, d, J = 1.8 Hz), 7.76 (1H, d, J = 6.6 Hz), 7.70 (1H, dd, J =6.6 Hz, J = 1.8 Hz), 7.50- 7 45 (1H, m), 7.35-7.28 (3H, m), 7.19 (1H, t,J = 6.6 Hz), 5.27 (2H, s), 4.31 (2H, t, J = 4.5 Hz), 2.78 (2H, t, J =4.5 Hz), 2.50 (4H, br), 2.36 (3H, s), 1.69 (4H, br) VIII-6

9.95 (1H, s), 8.62 (1H, brs), 8.58 (1H, s), 8.21 (1H, d, J = 6.9 Hz),7.94 (1H, d, J = 1.5 Hz), 7.77 (1H, d, J = 6.6 Hz), 7.69 (1H, d, J =6.9Hz), 7.51-7.45 (1H, m), 7.35-7.28 (3H, m), 7.19 (1H, t, J = 6.3 Hz),5.28 (2H, s), 4.32 (2H, t, J = 4.2 Hz), 3.09 (4H, brd, J = 4.5 Hz), 3.05(4H, brd, J = 4.5 Hz), 2.97-2.89 (4H, m), 1.13 (3H, t, J = 5.4 Hz)VIII-7

9.95 (1H, s), 8.61 (1H, brs), 8.58 (1H, s), 8.20 (1H, d, J = 6 6 Hz),7.94 (1H, brs), 7 77 (1H, d, J = 6.6 Hz), 7.69 (1H, d, J = 6.9 Hz),7.51-7.45 (1H, m), 7.35- 7.28 (3H, m), 7.19 (1H, t, J = 6.0 Hz), 5.27(2H, s), 4.32 (2H, t, J = 4.2 Hz), 3.59 (4H, t, J = 3.3 Hz), 2.91 (2H,q, J = 5.4 Hz), 2.68 (2H, t, J = 4.2 Hz), 1.13 (3H, t, J = 5.4 Hz)

TABLE 16 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-8

(E/Z mixture) 8.61 (0.5H, s), 8.58 (0.5H, s), 8.48 (0 5H, s), 8.25(0.5H, s), 7.99 (0.5H, d, J = 2.4 Hz), 7.97 (0.5H, d, J = 2.4 Hz), 7.90(0.5H, d, J = 7.9 Hz), 7.65-7.73 (2.5H, m), 7.50-7.55 (0 5H, m),7.26-7.34 (3.5H, m), 7.16 (1H, d, t J = 7.9, 2.4 Hz), 5.26 (2H, s), 4.29(1H, t, J = 7.0 Hz), 4.15 (1H, t, J = 7.0 Hz), 3.50-3.55 (1H, m),3.28-3.35 (2H, m), 3.20-3.28 (2H, m), 3.10-3.20 (2H, m), 2.99-3.07 (2H,m), 2.90- 2.96 (1H, m), 2.87-2.95 (1H, m), 1.21 (3H, d, J = 7.0 Hz),1.16 (3H, d, J = 7.0 Hz) VIII-9

(E/Z mixture) 8.58 (0.5H, s), 8.56 (0.5H, s), 8.44 (0.5H, s), 8 36 (05H, s), 7.99 (0.5H, d, J = 2.4 Hz), 7.97 (0.5H, d, J = 2.4 Hz), 7.90(0.5H, d, J = 7.9 Hz), 7.65-7.73 (2.5H, m), 7.50-7.55 (0.5H, m),7.26-7.34 (3.5H, m), 7.16 (1H, d, t J = 7.9, 2.4 Hz), 5.24 (2H, s), 4.21(1H, t, J = 7.0 Hz), 4.05 (1H, t, J = 7.0 Hz), 2.73 (1H, t, J = 7.2 Hz), 2.57 (1H, t, J = 7.2 Hz), 2.45-2 55 (2H, m), 2.30-2.35 (2H, m),1.64-1.70 (2H, m), 1.50-1.58 (2H, m), 1.21 (3H, d, J = 7.0 Hz), 1.16(3H, d, J = 7.0 Hz) VIII-10

(E/Z mixture) 10.09 (1H, s, major), 10.00 (1H, s, minor), 8.74 (1H, s,major), 8.59 (1H, s), 8.22 (1H, d, J = 9 Hz, major), 7.94-8.02 (1H, m),7.64-7.82 (2H, m), 7.44-7.52 (1H, m), 7.16-7.36 (4H, m), 5.27 (2H, s),4.32-4.43 (2H, m), 3.56-3.62 (4H, m), 2.66-2.74 (2H, m), 2.34 (3H, s,minor), 2.25 (3H, s, major) VIII-11

10.08 (1H, s), 8.74 (1H, s), 8.58 (1H, s), 8.22 (1H, d, J = 8.4 Hz),7.96 (1H, brs), 7.80 (1H, d, J = 8.4 Hz), 7.68 (1H, d, J = 9.6 Hz),7.43-7.52 (1H, m), 7.14- 7 36 (4H, m), 5.27 (2H, s), 4.37 (2H, t, J = 60 Hz), 2.80 (2H, t, J = 6.0 Hz), 2.25 (3H, s), 1.69 (4H, brs), 1.24 (4H,brs) VIII-12

(E/Z mixture) 9.95 (1H, s, major), 9.80 (1H, s, minor), 8.65 (1H, s,minor), 8.58 (1H, s, major), 8.54 (1H, s, major), 8.44 (1H, s, minor), 799 (1H, d, J = 1.5 Hz, minor), 7.91 (1H, d, J = 1.8 Hz, major), 7 15-792 (14H, m), 5.26 (2H, s), 5.25 (2H, s), 4.32 (2H, d, J = 3.9 Hz,major), 4.27 (2H, t, J = 4.2 Hz, minor), 2.82-3.06 (10H, m) VIII-13

(E/Z mixture) 9.96 (1H, s, major), 9.82 (1H, s, minor), 8.64 (1H, s,minor), 8.57 (1H, s, major), 8.53 (1H, brs, major), 8.44 (1H, brs,minor), 7.99 (1H, d, J = 2.7 Hz, minor), 7.90 (1H, d, J = 2.4 Hz,major), 7.14-7.88 (13H, m), 5.26 (2H, s, major), 5.24 (2H, s, minor), 432 (2H, t, J = 5.7 Hz, major), 4.27 (2H, t, J = 5 4 Hz, minor),3.53-3.58 (4H, m, major), 3.44- 3.50 (4H, m, minor), 2.56-2.70 (2H, m),2.32- 2.46 (4H, m)

TABLE 17 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-14

9.99 (1H, s), 8.65 (s, 1H), 8.61 (1H, s), 7.98 (1H, brs), 7.90 (1H, d, J= 6 9 Hz), 7.87 (1H, d, J = 6.9 Hz), 7.70 (1H, d, J = 6.3 Hz), 7.40-7.51(1H, m), 7.27- 7.35 (3H, m), 7.15-7.21 (1H, m), 5.27 (2H, s), 4.38 (2H,t, J = 3.9 Hz), 3.47-3.51 (4H, m), 2.57- 2.65 (2H, m), 2.33-2.40 (4H, m)VIII-15

9.94 (1H, s), 8.63 (1H, s), 8.58 (1H, s), 8.23 (1H, dd, J = 8.7 Hz, 1.2Hz), 7.96 (1H, d, J = 2.4 Hz), 7.76 (1H, d, J = 9.0 Hz), 7.70 (1H, dd, J= 8.4 Hz, 2.4 Hz), 7.44- 7.52 (1H, m), 7.28-7.35 (3H, m), 7.16-7.22 (1H,m), 5.27 (2H, s), 4.07-4.10 (2H, m), 3.23 (2H, t, J = 6.9 Hz), 3.01-3.04(6H, m), 2.38 (3H, s), 1.05 (3H, d, J = 6.3 Hz) VIII-16

9.94 (1H, s), 8.62 (1H, s), 8.58 (1H, s), 8.25 (1H, dd, J = 9.0 Hz, 1.5Hz), 7.95 (1H, d, J = 2.7 Hz), 7.76 (1H, d, J = 8.7 Hz), 7.69 (1H, dd, J= 8.7 Hz, 2.4 Hz), 7.44- 7.52 (1H, m), 7.28-7.35 (3H, m), 7.16-7.22 (1H,m), 5.27 (2H, s), 4.39-4.45 (1H, m), 3.25 (2H, t, J = 6.9 Hz), 2.95-3 01(5H, m), 2.73-2.92 (2H, m), 2 36 (3H, s), 1.30 (3H, d, J = 6.3 Hz)VIII-17

(di-HCl salt) 11.09 (1H, brs), 9.00 (1H, s), 8.90 (2H, brs), 8.75 (1H,s), 8.34 (1H, d, J = 9.3 Hz), 7.96 (1H, d, J = 2.7 Hz), 7.85 (1H, d, J =8.7 Hz), 7.72 (1H, dd, J = 9.0 Hz, 2.7 Hz), 7.45-7.52 (1H, m), 7.31-7.35(3H, m), 7.17-7.22 (1H, m), 5.29 (2H, s), 4.49 (2H, t, J = 5.4 Hz), 3.67(2H, t, J = 5.4 Hz), 3.49 (2H, q, J = 6.9 Hz), 3.21-3 23 (4H, m), 2.45(3H, s), 1.13 (3H, t, J = 6.9 Hz) VIII-18

9.93 (1H, s), 8.62 (1H, brs), 8.58 (1H, s), 8.22 (1H, d, J = 6 9 Hz),7.95 (1H, brs), 7.76 (1H, d, J = 6.0 Hz), 7.70 (1H, d, J = 6.3 Hz),7.50-7.45 (1H, m), 7.35- 7 28 (3H, m), 7.18 (1H, t, J = 5.4 Hz), 5.27(2H, s), 4.11-4 03 (2H, m), 2.87-2.67 (2H, m), 2.37 (3H, s), 1.85-1.76(1H, m), 1.73-1.59 (2H, m), 1.48-1.39 (1H, m) VIII-19

(bis-trifluoroacetate salt) 11.40 (1H, s), 9.10 (2H, s), 8.89 (1H, s),8.81 (1H, s), 8.42 (1H, d, J = 6.0 Hz), 7.90- 7.87 (2H, m), 7.62 (1H, d,J = 6.6 Hz), 7.51-7.46 (1H, m), 7.38-7.31 (3H, m), 7.20 (1H, t, J = 6.3Hz), 5 32 (2H, s), 4.48 (2H, brs), 3.61-3.46 (6H, m), 3.13 (3H, s), 2.97(2H, q, J = 5.7 Hz), 1.14 (3H, t, J = 5.7 Hz). VIII-20

(bis-trifluoroacetate salt) 11.07 (1H, s), 8.82 (1H, s), 8.78 (3H, brs),8.37 (1H, d, J = 6.6 Hz), 7.89-7.86 (2H, m), 7.64 (1H, d, J = 6.6 Hz),7.51-7.46 (1H, m), 7.36- 7.32 (3H, m), 7.20 (1H, t, J = 6.3 Hz), 5 31(2H, s), 4.45 (2H, brs), 2.97 (2H, q, J = 5.4 Hz), 2.67 (3H, brs), 1.13(3H, t, J = 5.4 Hz).

TABLE 18 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-21

(bis-trifluoroacetate salt) 11.03 (1H, s), 8.81 (1H, s), 8.78 (1H, s),8.71 (2H, s), 8.37 (1H, d, J = 6.6 Hz), 7.88-7.86 (2H, m), 7.64 (1H, d,J = 6.6 Hz), 7.51-7.46 (1H, m), 7.36-7.31 (3H, m), 7.20 (1H, t, J = 6.3Hz), 5.31 (2H, s), 4.46 (2H, brs), 3.39 (2H, brs), 3.10 (1H, brs), 2.97(2H, q, J = 6.3 Hz), 2.06 (2H, brd, J = 8.4 Hz), 1.78 (2H, brd, J = 8.4Hz), 1.37-1.04 (9H, m). VIII-22

9.95 (1H, s), 8.61 (1H, brs), 8.58 (1H, s), 8.19 (1H, d, J = 6.3 Hz),7.94 (1H, brs), 7.77 (1H, d, J = 6.6 Hz), 7.69 (1H, d, J = 6.6 Hz),7.50-7.45 (1H, m), 7.35- 7.28 (3H, m), 7.19 (1H, t, J = 6.0 Hz), 5.27(2H, s), 4.14-4.07 (2H, m), 3.43 (1H, br), 2.95-2.82 (4H, m), 1.86-1.80(1H, m), 1.69 (2H, m), 1.46 (1H, m), 1.14 (3H, t, J = 5.4 Hz) VIII-23

(E/Z mixture) 8.60 (0.5H, s), 8.58 (0.5H, s), 8.47 (0.5H, s), 8.39(0.5H, s), 7.96 (0.5H, d, J = 2.4 Hz), 7.93 (0.5H, d, J = 2.4 Hz), 7.88(0.5H, d, J = 7.9 Hz), 7.65-7.73 (2.5H, m), 7.50-7.55 (0.5H, m),7.26-7.34 (3.5H, m), 7.16 (1H, d, t J = 7.9, 2.4 Hz), 5.26 (2H, s), 4.19(1H, t, J = 7.0 Hz), 4.03 (1H, t, J = 7.0 Hz), 3.50-3.55 (1H, m),3.22-3.30 (1H, m), 3.16-3.23 (1H, m), 2.96-3.03 (1H, m), 3.04 (1.5H, s),2.90-2.95 (2H, m), 2.93 (1.5H, s), 2.70-2.80 (1H, m), 1.21 (3H, d, J =7.0 Hz), 1.16 (3H, d, J = 7.0 Hz) VIII-24

(E/Z mixture) 8.61 (0.5H, s), 8.59 (0.5H, s), 8.47 (0.5H, s), 8.41(0.5H, s), 7.99 (0.5H, d, J = 2.4 Hz), 7.97 (0.5H, d, J = 2.4 Hz), 7.90(0.5H, d, J = 7 9 Hz), 7.65-7.73 (2.5H, m), 7.50-7.55 (0.5H, m),7.26-7.34 (3.5H, m), 7.16 (1H, d, t J = 7.9, 2.4 Hz), 5.26 (2H, s), 4.29(1H, t, J = 7.0 Hz), 4.13 (1H, t, J = 7.0 Hz), 3.50-3.55 (1H, m), 3.14-330 (1H, m), 2.96-3.04 (1H, m), 2.54 (1.5H, s), 2.49 (1.5H, s), 1.21 (3H,d, J = 7.0 Hz), 1 16 (3H, d, J = 7 0 Hz), 1.00 (3H, t, J = 7.2 Hz)VIII-25

(E/Z mixture) 8.61 (0.5H, s), 8.58 (0.5H, s), 8.48 (0 5H, s), 8.31(0.5H, s), 7.99 (0.5H, d, J = 2.4 Hz), 7.97 (0.5H, d, J = 2.4 Hz), 7.90(0.5H, d, J = 7 9 Hz), 7 65-7.73 (2.5H, m), 7.50-7.55 (0.5H, m),7.26-7.34 (3.5H, m), 7.16 (1H, d, t J = 7.9, 2.4 Hz), 5 26 (2H, s), 4.29(1H, t, J = 7.0 Hz), 4.15 (1H, t, J = 7.0 Hz), 3.50-3.55 (1H, m),3.24-3.30 (1H, m), 3.10-3.14 (1H, m), 2.99 (1H, q, J = 7.2 Hz), 2.89(1H, q, J = 7.2 Hz), 1.21 (3H, d, J = 7.0 Hz), 1.16 (3H, d, J = 7.0 Hz),1.00 (3H, t, J = 7.2 Hz)

TABLE 19 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-26

(E/Z mixture) 8.61 (0.5H, s), 8.58 (0.5H, s), 8.48 (0.5H, s), 8.31(0.5H, s), 7.99 (0.5H, d, J = 2.4 Hz), 7.94 (0.5H, d, J = 2.4 Hz), 7 90(0 5H, d, J = 7.9 Hz), 7.65-7 73 (2.5H, m), 7.50-7 55 (0.5H, m),7.26-7.34 (3.5H, m), 7.16 (1H, d, t J = 7.9, 2.4 Hz), 5.26 (2H, s), 4.29(1H, t, J = 7.0 Hz), 4.11 (1H, t, J = 7.0 Hz), 3.50-3.55 (1H, m),3.14-3.17 (1H, m), 3.00-3.04 (1H, m), 2.00-2.10 (2H, m), 1.70-1.85 (2H,m), 1.00-1.30 (6H, m), 1.23 (3H, d, J = 7.0 Hz), 1.16 (3H, d, J = 7.0Hz) VIII-27

10.10 (1H, s), 8.76 (1H, s), 8.60 (1H, s), 8.25 (1H, d, J = 8.7 Hz),7.96 (1H, brs), 7.82 (1H, d, J = 9.0 Hz), 7.69 (1H, d, J = 9.0 Hz),7.43-7.52(1H, m), 7.14- 7.36 (4H, m), 5.28 (2H, s), 4.43 (2H, brs), 2.98(2H, brs), 2.54 (3H, s), 2.27 (3H, brs), 1.60 (1H, s) VIII-28

10.10 (1H, s), 8.77 (1H, s), 8.60 (1H, s), 8.25 (1H, d, J = 8.7 Hz),7.95 (1H, brs), 7.82 (1H, d, J = 9.6 Hz), 7.69 (1H, d, J = 9.3 Hz),7.43-7.52 (1H, m), 7.14- 7.36 (4H, m), 5.28 (2H, s), 4.45 (2H, brs),2.91 (2H, brs), 2.27 (3H, s), 2.00 (2H, brs), 1.73 (2H, brs), 1.60 (1H,brs), 1.23 (7H, brs) VIII-29

(E/Z mixture) 9.94 (1H, s, major), 9.78 (1H, s, minor), 8.62 (1H, s,minor), 8.56 (1H, s, major), 8.51 (1H, brs, major), 8.42 (1H, brs,minor), 7.12- 7.53 (14H, m), 5.24 (2H, s,), 4.15-4.28 (2H, m), 3.13-3.25 (2H, m), 2.80-3.00 (7H, m) VIII-30

9.93 (1H, s), 8.62 (1H, brs), 8.58 (1H, s), 8.22 (1H, d, J = 6.3 Hz),7.96 (1H, d, J = 1.2 Hz), 7.76 (1H, d, J = 6.6 Hz), 7.70 (1H, d, J = 6.6Hz), 7.50-7.45 (1H, m), 7.35-7.28 (3H, m), 7.19 (1H, t, J = 6.6 Hz),5.27 (2H, s), 4.23 (1H, dd, J = 8.1 Hz, J = 4.2 Hz), 4.11 (1H, dd, J =8.1 Hz, J = 4.2 Hz), 2.98-2.93 (1H, m), 2.59- 2.54 (1H, m), 2.36 (6H,s), 2.17 (1H, dd, J = 13 Hz, J = 6.6 Hz), 1.97-1.88 (1H, m), 1.71-1.54(3H, m) VIII-31

9.92 (1H, s), 8.62 (1H, brs), 8.58 (1H, s), 8.22 (1H, d, J = 6.9 Hz),7.96 (1H, brs), 7.76 (1H, d, J = 6.6Hz), 7.70 (1H, d, J = 6.6 Hz),7.50-7.45 (1H, m), 7.35- 7.28 (3H, m), 7.19 (1H, t, J = 6.6 Hz), 5.27(2H, s), 4.18 (1H, dd, J = 7.8 Hz, J = 4.5 Hz), 4.06 (1H, dd, J = 7.8Hz, J = 4.5 Hz), 3.43 (1H, t, J = 4.8 Hz), 3.24 (3H, s), 3.08-2.99 (2H,m), 2.88-2.81 (1H, m), 2.36 (3H, s), 2.27 (1H, dd, J = 13 Hz, J = 6.6Hz), 1.93-1.84 (1H, m), 1.72-1.54 (3H, m)

TABLE 20 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-40

10.08 (1H, bs), 8.74 (1H, s), 8.58 (1H, s), 8.21 (1H, d, J = 8.8 Hz),7.96 (1H, s), 7.80 (1H, d, J = 8.8 Hz), 7.51-7.45 (1H, m), 7.35-7.27(3H, m), 7.19 (1H, t, J = 8.0 Hz), 5.27 (2H, s), 4.04 (2H, t, J = 5.6Hz), 3.08-3.05 (1H, m), 2.22 (3H, s), 1.04 (3H, d, J = 6.4 Hz). VIII-41

10.13-10.09 (1H, m), 8.82 (1H, s), 8.74 (1H, s), 8.21 (1H, d, J = 14.0Hz), 7 69-7.62 (1H, m), 7.50-7.45 (1H, m), 7 35-7 26 (3H, m), 7.18 (1H,t, J = 8.2 Hz), 5.27 (2H, s), 4 69 (1H, bs), 4.25-4.21 (1H, m),4.13-4.09 (1H, m), 3.46-3.44 (2H, m), 3.09 (1H, t, J = 5.6 Hz), 2.26(3H, s) VIII-42

10.2 (1H, s), 8.78 (1H, s), 8.59 (1H, s), 8.24 (1H, d, J = 8.8 Hz), 7.96(1H, s), 7.81 (1H, d, J = 8.8 Hz), 7.66-7.73 (1H, m), 7.43-7.50 (1H, m),7 23-7.36 (3H, m), 7 15-7.22 (1H, m), 5.27 (2H, s), 4.31-4.48 (2H, m),3.07-3 15 (2H, m), 2.27 (3H, s) VIII-43

10.10 (1H, brs), 8.75 (1H, d, J = 2.0 Hz), 8.59 (1H, s), 8.17 (1H, dd, J= 2.4, 11.6 Hz), 7.96 (1H, d, J = 3.2 Hz), 7.80 (1H, d, J = 12.0 Hz),7.68 (1H, dd, J = 3.6, 12.0 Hz), 7.51-7.44 (1H, m), 7.34-7.26 (3H, m),7.22-7.15 (1H, m), 5.27 (2H, s), 4.94 (2H, s), 3.71 (3H, s), 2.27 (3H,s) VIII-44

(CDCl3) 8.71 (1H, s), 8.53 (1H, s), 8.39 (1H, s), 8.23 (1H, d, J = 9.0Hz), 7.88 (1H, d, J = 9.0 Hz), 7.81 (1H, d, J = 2.4 Hz), 7.57 (1H, dd, J= 2.4, 9.0 Hz), 7.40-7.33 (1H, m), 7.26-7.21 (2H, m), 7.06-6.97 (2H, m),5.17 (2H, s), 4.49 (2H, t, J = 5.4 Hz), 3.40 (2H, d, J = 6.0 Hz), 3.25(3H, s), 3.14-2.98 (3H, m), 2.25 (3H, s), 1.06 (3H, d, J = 6.6 Hz).VIII-45

(di-HCl salt) 12.2 (1H, s), 9.61 (2H, brs), 9.38 (1H, s), 8.93 (1H, s),8.46 (1H, d, J = 8.8 Hz), 8.03 (1H, d, J = 8.4 Hz), 7.93 (1H, d, J = 2.4Hz), 7.69 (1H, dd, J = 8.8 Hz, J = 2.4 Hz), 7.44-7.52 (1H, m), 7.30-7.36(3H, m), 7.15-7.23 (1H, m), 5.32 (2H, s), 4.61 (2H, brs), 3.65-3.70 (2H,m), 3 45-3.56 (5H, m), 3.12 (3H, s). 2.28 (3H, s) VIII-46

10.07 (1H, brs), 8.73 (1H, s), 8.58 (1H, s), 8.21 (1H, d, 6.6 Hz), 7.96(1H, s), 7.79 (1H, d, J = 6.6 Hz), 7.68 (1H, d, J = 6.6 Hz), 7.49-7 44(1H, m), 7.34-7.25 (3H, m), 7.19-7.15 (1H, m), 5.26 (2H, s), 4.31 (2H,t, 4.5 Hz), 2.95 (2H, t, 4 5 Hz), 2.25 (3H, s), 2.16 (1H, m), 0.36 (2H,m), 0.25 (2H, m) VIII-47

(di-HCl salt) 12.26 (1H, brs), 9.36 (1H, s), 8.91 (1H, s), 8.45 (1H, d,6.6 Hz), 8.29 (1H, m), 8.00 (1H, d, J = 6.6 Hz), 7.91 (1H, s), 7.68 (1H,d, J = 6.6 Hz), 7.51-7.45 (1H, m), 7.36-7.31 (3H, m), 7.23-7.17 (1H, m),5.32 (2H, s), 4.59 (2H, m), 3.48 (2H, m), 3 41 (2H, m), 3.10 (2H, m),2.28 (3H, s), 1.82 (3H, s)

TABLE 21 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-48

(di-HCl salt) 12.49 (1H, brs), 9.43 (1H, s), 8 93 (1H, s), 8.43 (1H, d,6.6 Hz), 8.09 (1H, d, J = 6.6 Hz), 7.93 (1H, s), 7.70 (1H, d, J = 6.6Hz), 7.51-7.45 (1H, m), 7.36-7.31 (3H, m), 7.23-7.17 (1H, m), 5.32 (2H,s), 4.61 (2H, m), 4.24 (1H, m), 3.80 (1H, m), 3.68 (1H, m), 3.49 (2H,m), 3.20 (1H, m), 3.05 (1H, m), 2.28 (3H, s), 1.99 (1H, m), 1.83 (2H,m), 1.58 (1H, m) VIII-49

(di-HCl salt) 12.44 (1H, brs), 9.41 (1H, s), 8.92 (1H, s), 8.43 (1H, d,6.6 Hz), 8.08 (1H, d, J = 6.6 Hz), 7.92 (1H, s), 7.70 (1H, d, J = 6.6Hz), 7.51-7.45 (1H, m), 7.36-7.31 (3H, m), 7.23-7.16 (1H, m), 5.31 (2H,s), 4.61 (2H, m), 4.24 (1H, m), 3.80 (1H, m), 3.68 (1H, m), 3.48 (2H,m), 3.19 (1H, m), 3.05 (1H, m), 2.28 (3H, s), 1.99 (1H, m), 1.84 (2H,m), 1.58 (1H, m). VIII-50

(di-HCl salt) 12.37 (1H, brs), 9 41 (1H, s), 8.91 (1H, s), 8.41 (1H, d,6.0 Hz), 8.04 (1H, d, J = 6 0 Hz), 7.91 (1H, s), 7.68 (1H, d, J = 6 0Hz), 7.45 (1H, m), 7.36-7.31 (3H, m), 7.20-7.14 (1H, m), 5 29 (2H, s),4.58 (2H, m), 3.44 (2H, m), 3 31 (2H, m), 3.22 (2H, m), 2.95 (2H, m),2.27-1.55 (9H, m) VIII-51

(di-HCl salt) 10.07 (1H, brs), 8.74 (1H, s), 8.58 (1H s), 8.20 (1H, d,6.6 Hz), 7.96 (1H, s), 7.79 (1H, d, J = 6.6 Hz) 7.69 (1H, d, J = 6.6Hz), 7.66 (1H, s), 7.49-7.43 (1H, m), 7.34-7.24 (3H, m), 7.19-7.15 (1H,m), 5.26 (2H, s), 4.32 (2H, m), 3.61 (1H, m), 2.93 (2H, m), 2.61 (2H, d,4.5 Hz), 2.25 (3H, s), 2.09 (3H, m), 1.70 (H, m) VIII-52

10.07 (1H, brs), 8.74 (1H, s), 8 58 (1H, s), 8 20 (1H, d, 6.6 Hz), 7.96(1H, s), 7.79 (1H, d, J = 6.6 Hz) 7.69 (1H, d, J = 6.6 Hz), 7.66 (1H,s), 7.49-7.43 (1H, m), 7.34-7.24 (3H, m), 7.19-7.15 (1H, m), 5 26 (2H,s), 4.32 (2H, m), 3.61 (1H, m), 2.93 (2H, m), 2.61 (2H, d, 4.5 Hz), 2.25(3H, s), 2.09 (3H, m), 1.70 (1H, m) VIII-53

(di-HCl salt) 12 04 (1H, brs), 9.26 (1H, s), 8.91 (1H, s), 8.45 (1H, d,10.5 Hz), 7.99 (1H, d, 9.0 Hz), 7.91 (1H, s), 7.67 (1H, d, J = 9.0 Hz),7.53-7.45 (1H, m), 7 37-7.31 (3H, m), 7.23-7.17 (1H, m), 6.65 (2H, s), 532 (2H, s), 4.58 (2H, m), 4.23 (2H, m), 3.50 (2H, m), 3.30 (2H, m), 2.28(3H, s) VIII-54

(tri-HCl salt) 10.88 (1H, bs), 9.68 (1H, bs), 9.33 (1H, s), 8.83 (1H,s), 8.61 (1H, bs), 8.54 (2H, d, J = 5.2 Hz), 8.00 (1H, d, J = 7.96 Hz),7.95 (1H, s), 7.71 (1H, d, J = 8.4 Hz), 7.49-7.45 (1H, m), 7.33 (2H, d,J = 5.6 Hz), 7.24-7.17 (1H, m), 5.31 (2H, s), 4.61 (2H, bs), 2 91 (2H,bs), 2.68 (3H, s), 2.37-2.33 (2H, m), 2.29 (3H, s), 2 05-1.79 (5H, m),1.24 (2H, s).

TABLE 22 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-55

10.07(1H, bs), 8.74(1H, s), 8.59(1H, s), 8.31(1H, s), 8.21(1H, d, J =8.8 Hz), 7.96(1H, s), 7.80(1H, d, J = 8.4 Hz), 7.69(1H, d, J = 9.2 Hz),7.50-7.45 (3H, m), 7.18(1H, t, J = 6.4 Hz), 5.27(2H, s), 4.33-4.30(2H,m), 3.81(2H, d, J = 7.2 Hz), 2.93 (2H, t, J = 5.9 Hz), 2.67-2.65(1H, m),2.33(3H, s), 1.76(2H, d, J = 11.6 Hz), 1.24-1.16(4H, m). VIII-56

10.08(1H, s), 8.75(1H, s), 8.59(1H, s), 8.21(1H, d, J = 10.0 Hz),7.80(1H, d, J = 10.0 Hz), 7.69(1H, d, J = 8.4 Hz), 7.47(1H, t, J = 6.8Hz), 7.35-7.17(4H, m), 5.27(2H, s), 3.29(3H, s), 3 08-2.93(1H, m),2.41(3H, s), 2.26(3H, s). VIII-57

10 1(1H, s), 8.75(1H, s), 8.59(1H, s), 8.22(1H, d, J = 8.4 Hz), 7.96(1H,s), 7.80(1H, d, J = 8.8 Hz), 7.69(1H, d, J = 8.8 Hz), 7.43-7.51(1H, m),7.23-7.36(3H, m), 7.18(1H, t, J = 6.4 Hz), 5 27(2H, s), 4.33(2H, t, J =5.6 Hz), 3.30-3.33(2H, m), 2.98-3.05(2H, m), 2.25(3H, s) VIII-58

10.1(1H, s), 8.75(1H, s), 8.59(1H, s), 8.23(1H, d, J = 8.8 Hz), 7.96(1H,s), 7.80(1H, d, J = 8.8 Hz), 7.74(1H, d, J = 8.8 Hz), 7.43-7.50(1H, m),7.25-7.35(3H, m), 7.18(1H, t, J = 7.6 Hz), 6.99-7.08(2H, m), 5.27(2H,s), 4 35(2H, t, J = 5.6 Hz), 3.48-3.53(2H, m), 2.68(3H, d, J = 4.4 Hz),2.26(3H, s) VIII-59

(di-HCl salt) 11.83(1H, brs), 9.02(1H, s), 8.93(1H, s), 8 45(1H, d, J =8.7 Hz), 7 89(1H, d, 8.7 Hz), 7.87(1H, d, J = 2.4 Hz), 7.62(1H, dd, J =2.4 Hz, J = 9.0 Hz), 7.53-7.45(1H, m), 7.38-7.31(3H, m), 7.82-7.20(1H,m), 5 32(2H, s), 4.37(2H, m), 3.56-3.25(10 H, m), 2.26(3H, s) VIII-60

10.08(1H, s), 8.74(1H, s), 8.59(1H, s), 8.22(1H, d, J = 8.8 Hz),7.76(1H, s), 7.81(1H, d, J = 8.8 Hz), 7.69(1H, d, J = 7.2 Hz), 7.47(1H,t, J = 7.2 Hz), 7.35-7 27(2H, m), 7.22-7.17(1H, m), 5.27(2H, s),4.31-4.26(2H, m), 3.51-3.44(2H, m), 2.93-2.88 (2H, m), 2.83(3H, s), 263-2.59(1H, m), 2.26 (3H, s), 1.91-1.88(2H, m), 1.33-1.24(2H, m).VIII-61

10.07(1H, s), 8.75(1H, s), 8.59(1H, s), 8.21(1H, d, J = 7.2 Hz),7.96(1H, s), 7.80(1H, d, J = 7.2 Hz), 7.69(1H, d, J = 8.8 Hz), 7.48(1H,dd, J = 8.4 Hz), J = 7.2 Hz), 7 34-7.27(3H, m), 7.18(1H, t, J = 7.2 Hz),5 27(2H, s), 4.32(2H, t, J = 6.8 Hz), 4.15(1H, bs), 3.72(1H, d, J = 12.8Hz), 3.05(1H, t, J = 10.8 Hz), 2 94(1H, t, J = 5.6 Hz), 2.26(3H, s),1.97(3H, s), 1.24(2H, bs).

TABLE 23 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-62

(di-HCl salt) 12 14(1H, bs), 9.16-9.08(1H, m), 8 91(2H, s), 8.44(1H, d,J = 8.0 Hz), 8.91(2H, s), 8 44(1H, d, J = 8.0 Hz), 8.02(1H, d, J = 8.8Hz), 7 91(1H, s), 7.68(1H, d, J = 8.4 Hz), 7.51-7.46(1H, m),7.37-7.31(2H, m), 7.21-7.18(1H, m), 5.32(2H, s), 4.62(2H, bs),3.44-3.38(2H, m), 3.32-3 21(2H, m), 3.08-3.07(1H, m), 2.99-2.91(1H, m),2.28(3H, s), 2.08-2.02(1H, m), 1.24-1.19(1H, m), 0.91(3H, d, J = 6.4Hz). VIII-63

10.08(1H, s), 8.75(1H, s), 8.68(1H, s), 8.22(1H, d, J = 8.8 Hz), 779(1H, s), 7.80(1H, d, J = 7.2 Hz), 7.70(1H, d, J = 8.8 Hz),7.50-7.45(1H, m), 7.35-7.27(3H, m), 7.18(1H, t, J = 8.8 Hz), 5.27(2H,s), 4.34(2H, t, J = 5.6 Hz), 3.35-3.32(2H, m), 2.92(2H, t, J = 5.6 Hz),2.65-2.61(1H, m), 2.26(3H, s), 1 75-1.70(1H, bs), 0.84(3H, d, J = 5.6Hz). VIII-64

10.09(1H, s), 8.58(1H, s), 8.22(1H, dd, J = 8.7 Hz, 1.8 Hz), 7.95(1H, d,J = 2.7 Hz), 7.80(1H, d, J = 9.0 Hz), 7.68(1H, dd, J = 8.7 Hz, 2.7 Hz),7.51-7.44(1H, m), 7.35-7.16(4H, m), 3.22(3H, s), 2.77(2H, t, J = 5.7Hz), 2.60(2H, t, J = 5.7 Hz), 2.29(3H, s), 2.24(3H, s). VIII-65

10.09(1H, bs), 8.74(1H, s), 8.58(1H, s), 7.96(1H, d, J = 2.1 Hz),7.80(1H, d, J = 8.7 Hz), 7.68(1H, d, J = 9.0 Hz), 7.48(1H, dd, J = 8.1Hz), 7.35-7.26(3H, m), 7.19(1H, t, J = 8.1 Hz), 5.27(2H, s), 4.32(2H, t,J = 6.0 Hz), 3.23(3H, s), 2.86(2H, t, J = 6.0 Hz), 2.87-2.59(4H, m),2.24(3H, s), 0.98(3H, t, J = 7.2 Hz). VIII-66

(di-HCl salt) 10.70(1H, brs), 9.92(1H, brs), 8.94(1H, s), 8.69(1H, s),8.30(1H, d, J = 12), 7.95-7.94(1H, m), 786(1H, d, J = 12), 7.71-7.68(1H,m), 7.52-7.44(1H, m), 7.35-7.28(3H, m), 7.22-7.15(1H, m), 5.40(1H, br),5.30(2H, s), 4.74-4.60(2H, m), 3.83-3.75(2H, m), 3.70-3.55(2H, m),2.92(3H, s), 2.28(3H, s) VIII-67

10.09(1H, s), 8.75(1H, s), 8.59(1H, s), 8.22(1H, d, J = 8.7 Hz),7.95(1H, d, J = 2.1 Hz), 7.81(1H, d, J = 9.0 Hz), 7.69(1H, d, J = 8.7Hz), 7.51-7.34(1H, m), 7.34-7.26(2H, m), 7.21-7.16(1H, m), 5.27(2H, s),4 34(2H, t, J = 6.3 Hz), 2.96(2H, t, J = 6.9 Hz), 2.56(3H, s), 2.26(3H,s). VIII-68

10.4(1H, s), 9.06(1H, s), 8.59(1H, s), 8.30(1H, d J = 8 Hz), 8.01(1H,s), 7.81(1H, d, J = 8.8 Hz), 7.74(1H, d, J = 8.8 Hz), 7.44-7.50(1H, m),7.24-7.36(3H, m), 7.18(1H, t, J = 7.2 Hz), 5.27(2H, s), 4.21-4.36(4H,m), 3.98-4.04(1H, m), 2.25(3H, s)

TABLE 24 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-69

(di-HCl salt) 9.37(1H, s), 8.91(1H, s), 8.42(1H, d, 7.8 Hz), 8.00(1H, d,J = 6.6 Hz), 7.92(1H, s), 7.69(1H, d, J = 7.8 Hz), 7.51-7.45(1H, m),7.36-7.31(3H, m), 7.22-7.17(1H, m), 5.32(2H, s), 4.75-4.60(2H, m),3.85-3.10(7 H, m), 2.27(3H, s), 2.15-1.74(4H, m) VIII-70

10.07(1H, bs), 8.74(1H, bs), 8.59(1H, s), 8.22 (1H, d, J = 8.8 Hz),7.98-7.96(2H, m), 7.80(1H, d, J = 8.8 Hz), 7.68(1H, d, J = 8.8 Hz),7.50-7.45(1H, m), 7.35-7.27(3H, m), 7.20-7.16(1H, m), 5.27 (2H, s),4.37(2H, t, J = 5.6 Hz), 4.16(1H, bs), 2.79-2.66(4H, m), 2.46-2.42(3H,m), 2.25(3H, s), 2.06(1H, bs), 1.78(3H, s), 1.56-1.51(1H, m). VIII-71

(di-HCl salt) 9.29(1H, m), 8.91(1H, s), 8.42(1H, m), 7.99(1H, d, 8.7Hz), 7.92(1H, s), 7.67(1H, d, J = 9.0 Hz), 7.53-7.45(1H, m),7.37-7.31(3H, m), 7.23-7.17(1H, m), 6.68(2H, brs), 5.32(2H, s), 5.11(1H,m), 4.66(3H, m), 3.72-3.70(5 H, m), 3.51(1H, m), 3.26(2H, m), 2.28(3H,s) VIII-72

10.08(1H, bs), 8.74(1H, s), 8.56(1H, s), 8.21(1H, d, J = 8.0 Hz),7.93(1H, s), 7.79(1H, d, J = 8.8 Hz), 7.67-7.65(1H, m), 7.50-7 40(1H,m), 7.33-7.24 (2H, m), 7.20-7.12(1H, m), 5.25(2H, s), 4.36-4.30 (1H, m),4.22-4.17(1H, m), 4.08-3.92(2H, m), 2.98(2H, bs), 2.24(3H, s),2.00-1.90(1H, m), 1.80-1.70(2H, m), 1.62-1 52(1H, m) VIII-73

10.08(1H, bs), 8.80(1H, s), 8.57(1H, s), 8.21(1H, d, J = 8.8 Hz),7.97(1H, s), 7.79(1H, d, J = 8.8 Hz), 7 71-7.68(1H, m), 7.46(1H, dd, J =8.0, J = 14.4), 7 34-7 25(2H, m), 7.19-7 15(1H, m), 5 26(2H, s),4.22-4.20(2H, m), 2.98-2.84(2H, m), 2.25(2H, s), 1.92-1.82(1H, m),1.79-1.62(2H, m), 1.54-1.45(1H, m). VIII-74

10.07(1H, bs), 8.74(1H, s), 8.58(1H, s), 8.21(1H, d, J = 8.4 Hz),7.95(1H, s), 7.79(1H, d, J = 8.8 Hz), 7.69-7.67(1H, m), 7.47(1H, dd, J =8.4, J = 15.2), 7.34-7.26(2H, m), 7.19-7.15(1H, m), 5.26(2H, s),4.23-4.13(2H, m), 3.43(2H, t, J = 6.0), 3.23(3H, s), 3.11-3.03(2H, m),2.91-2.86(1H, m), 2.53-2.47(1H, m), 2.30-2.24(1H, m), 2.24(3H, s),1.90-1.83(1H, m), 1.72-1.67(2H, m), 1.59-1.53(1H, m). VIII-75

10.07(1H, s), 8.73(1H, s), 8.57(1H, s), 8.20(1H, d, J = 8.8 Hz),7.95-7.94(1H, m), 7.79(1H, d, J = 8.8 Hz), 7.68-7.63(1H, m), 7.46(1H,dd, J = 8.0, J = 14.0), 7 33-7.25(2H, m), 7.19-7.14(1H, m), 5.26(2H, s),4.27-4.18(2H, m), 2.95-2.92(1H, m), 2.62-2.57(1H, m), 2.41(3H, s),2.23(3H, s), 2.19-2.15(1H, m), 1.96-1.87(1H, m), 1.74-1.61(2H, m), 159-1.53(1H, m).

TABLE 25 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-76

10.09(1H, bs), 8.76(1H, d, J = 1.8 Hz), 8.58(1H, s), 8.22(1H, dd, J =1.8 Hz, J = 8.7 Hz), 7.96(1H, d, J = 2.4 Hz), 7.87-7.78(2H, m), 7.68(1H,dd, J = 2.1 Hz, J = 9.0 Hz), 7.52-7.44(1H, m), 7.35-7.26(3H, m), 7.22-716(1H, m), 5.27(2H, s), 4.57-4.49(1H, m), 4.35-4.27(2H, m),3.77-3.71(1H, m), 2.26(3H, s), 1.36(3H, d, J = 6.3 Hz). VIII-77

10.08(1H, bs), 8.75(1H, d, J = 1.8 Hz), 8.58(1H, s), 8.22(1H, dd, J =1.8 Hz, J = 9.0 Hz), 7.96(1H, d, J = 2.4 Hz), 7.80(1H, d, J = 9.0 Hz),7.76(1H, dd, J = 2.4 Hz, J = 9.0 Hz), 7.51-7.44(1H, m), 7.35-7.26(3H,m), 7.21-7.15(1H, m), 5.26(2H, s), 4 85-4.76(1H, m), 4.39(1H, dd, J =5.7 Hz, J = 11.4 Hz), 4.30(1H, dd, J = 4.5 Hz, J = 11.4 Hz), 4 11-407(1H, m), 2.25(3H, s), 1.40(3H, d, J = 6.6 Hz). VIII-78

10.07(1H, brs), 8.74(1H, s), 8.58(1H, s), 8.21(1H, d, 9.0 Hz), 7.97(1H,s), 7.82-7.78(2H, m), 7.69(1H, d, 9.0 Hz), 7.51-7.44(1H, m),7.35-7.26(3H, m), 7.22-7.15(1H, m), 5.27(2H, s), 4.24(2H, d, 4.8 Hz),3.91(1H, m), 2.31-2.06(6 H, m), 1.95-1.87(1H, m) VIII-79

10.09(1H, s), 8.74(1H, s), 8.59(1H, s), 8.21(1H, d, J = 8.8 Hz),7.97(1H, s), 7.91-7.89(1H, m), 7.80(1H, d, J = 8.4 Hz), 7.69(1H, d, J =8.8 Hz), 7 51-7.45(1H, m), 7.35-7.27(3H, m), 7.20-7.17(1H, m), 5 27(2H,s), 4.26-4.06(3H, m), 3.46(1H, t, J = 6.8 Hz), 3.02-2.98(1H, m),2.58(1H, dd, J = 12.0 Hz, J = 5.6 Hz), 2.26(3H, s), 2.20-2.10(1H, m),1.77(3H, m), 1.38-1.31(1H, m). VIII-80

10.3(1H, s), 8.95(1H, s), 8.57(1H, s), 8.22(1H, d, J = 9.6), 8.01(1H,s), 7.80-7.73(2H, m), 7.47-7.41(1H, m), 7.34-7.25(2H, m), 7.20-7.12(1H,m), 5 37(1H, br), 5.26(2H, s), 5.10(1H, brs), 3.78-3.48(5 H, m),2.45-2.35(1H, m), 2 26(3H, s), 2.05-1.96(1H, m). VIII-81

10 45(1H, s), 8.92(1H, s), 8.65(1H, s), 8.31(1H, d, J = 8.4 Hz),7.97(1H, s), 7.77(1H, d, J = 8.8 Hz), 7.71(1H, d, J = 9.2 Hz),7.51-7.45(1H, m), 7 35-7.28(2H, m), 7.19(1H, t, J = 8.4 Hz), 5 28(2H,s), 4.56-4.47(3H, m), 4.15(1H, bs), 3.60(1H, bs), 3.12(1H, bs), 2.28(3H,s), 2.09(1H, dd, J = 13.2 Hz, J = 6.0 Hz), 1.862-1.81(1H, m). VIII-82

10.08(1H, s), 8.75(1H, s), 8.59(1H, s), 8.22(1H, d, J = 8.8 Hz),7.97(1H, s), 7.80(1H, d, J = 8.8 Hz), 7.69(1H, d, J = 8.0 Hz), 7 51-745(1H, m), 7.35-7.27(m, 3 H), 7.20-7.17(1H, m), 5.27(2 H s), 4.67(1H,bs), 4 29-4.19(3H, m), 3.45-4.40(1H, m), 2.88(1H, dd, J = 11.2 Hz, J = 56 Hz), 2.70(1H, dd, J = 11.0, J = 3.6 Hz), 2.27(3H, s), 2.10-2.02(1H,m), 1.46-1.39(1H, m).

TABLE 26 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-83

10.07(1H, brs), 8.74(1H, s), 8.58(1H, s), 8.21(1H, d, 8.7 Hz), 7.97(1H,s), 7.82-7.78(2H, m), 7.69(1H, d, 9.0 Hz), 7.51-7.44(1H, m),7.35-7.26(3H, m), 7.22-7.15(1H, m), 5.27(2H, s), 4.24(2H, d, 4.8 Hz),3.91(1H, m), 2.31-2.06(6 H, m), 1.95-1.87(1H, m) VIII-84

10.35(1H, s), 9 08(1H, s), 8.60(1H, s), 8.40(1H, s), 8.22(1H, d, J = 8.4Hz), 8.09(1H, s), 7.83-7.82(2H, m), 7.49-7.47(1H, m), 7.33-7.19(4H, m),5.27(2H, s), 4.43-4.16(4H, m), 3.01-2.98(2H, M), 2 28(3H, s), 1.92(2H,bs), 1.83(3H, s). VIII-85

10.1(1H, brs), 8.82(1H, s), 8.58(1H, s), 8.21(1H, d, J = 8.8), 7.98(1H,s), 7.80(1H, d, J = 8.4), 7.72-7.70(1H, m), 7.50-7.44(1H, m),7.34-7.26(3H, m), 7.20-7.15(1H, m), 5.26(2H, s), 4.22(2H, s), 3.57(1H,br), 2.96-2.89(2H, m), 2.26(3H, s), 1.98-1.62(3H, m), 1.58-1.45(1H, m).VIII-86

10.07(1H, bs), 8.75(1H, s), 8.57(1H, s), 8.21(1H, d, J = 8.8 Hz),7.95(1H, s), 7.79(1H, d, J = 8.8 Hz), 7.71-7.68(1H, m), 7.50-7.44(1H,m), 7.34-7.26(2H, m), 7.19-7.15(1H, m), 5.26(2H, s), 4.22-4.20(2H, m),3.03-2.95(2H, m), 2.26(3H, s), 2.02-1.93(1H, m), 1.80-1.73(2H, m),1.62-1.56(1H, m) VIII-87

10.0(1H, brs), 8.73(1H, s), 8.57(1H, s), 8.19(1H, d, J = 9.2), 7.95(1H,s), 7.79(1H, d, J = 8.8), 7 69-7 67(1H, m), 7.50-7.44(1H, m),7.34-7.26(3H, m), 7 20-7.16(1H, m), 5.26(2H, s), 4.24-4.17(2H, m), 377(1H, d, J = 17.2), 3.58(1H, s), 3.50(1H, d, J = 17.6), 3.22-3.12(1H,m), 3.10-3.00(1H, m), 2.58-2.52(1H, m), 2.23(3H, s), 1 98-1.89(1H, m),1.77-1.70(2H, m), 1.59-1.52(1H, m). VIII-88

10.8(1H, s), 8.98(1H, s), 8.58(1H, s), 8.20-8.16(2H, m), 7.91-7.88(1H,m), 7.80(1H, d, J = 7 6), 7.50-7.44(1H, m), 7 34-7.30(2H, m), 7 23(1H,d, J = 8.8), 7.20-7.15(1H, m), 5.26(2H, s), 4 23-4.41(2H, m), 3.76(1H,d, J = 16.4), 3.52(1H, d, J = 16.4), 3.61-3.52(1H, m), 3.45-3 36(1H, m),2 91-2 85(1H, m), 2.25(3H, s), 2 09-2.02(1H, m), 1 91-1 79(2H, m),1.73-1.66(1H, m). VIII-89

10.87(1H, s), 8.97(1H, s), 8.58(1H, s), 8.20-8 15(2H, m), 7.91-7 88(1H,m), 7.80(1H, d, J = 8.8), 7.50-7.44(1H, m), 7 34-7.30(2H, m), 7.23(1H,d, J = 8.8), 7.20-7.15(1H, m), 5.26(2H, s), 4.22-4.41(2H, m), 3.76(1H,d, J = 16.4), 3.52(1H, d, J = 16.4), 3.61-3.52(1H, m), 3.45-3.36(1H, m),2.91-2.85(1H, m), 2.25(3H, s), 2.09-2 02(1H, m), 1.91-1 79(2H, m),1.73-1.66(1H, m).

TABLE 27 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-90

10.0(1H, s), 8.72(1H, s), 8.56(1H, s), 8.21-8.19(1H, m), 7.93(1H, s),7.80-7.78(1H, m), 7.67-7.65(1H, m), 7.49-7.42(1H, m), 7.33-7.25(3H, m),7.19-7.14(1H, m), 5.26(2H, s), 4.40(1H, brs), 4.27-4.19(1H, m),4.16-4.09(1H, m), 3.10-2.94(2H, m), 2.90-2.80(1H, m), 2.23(3H, s),1.93-1.82(1H, m), 1.75-1.62(2H, m), 1.61-1.52(1H, m). VIII-91

10.08(1H, s), 8.74(1H, s), 8.56(1H, s), 8.21(1H, d, J = 8.8 Hz),7.93(1H, s), 7.89(1H, d, J = 8.8 Hz), 7.68-7.63(1H, m), 7.46(1H, dd, J =8.0, J = 14.0), 7.33-7.24(2H, m), 7.19-7.14(1H, m), 5.25(2H, s),4.27-4.18(2H, m), 2.95-2.92(1H, m), 2.62-2.57(1H, m), 2.41(3H, s),2.23(3H, s), 2.46-2.39(1H, m), 2.04-1 95(1H, m), 1.78-1.73(2H, m),1.65-1.56(1H, m) VIII-92

10.0(1H, s), 8.72(1H, s), 8.57(1H, s), 8.21(1H, d, J = 8.4), 7.94(1H,s), 7.79(1H, d, J = 8.8), 7.68-7.66(1H, m), 7.49-7.44(1H, m),7.34-7.25(3H, m), 7.19-7.15(1H, m), 5.26(2H, s), 4.93(1H, brs), 3.02(1H,d, J = 10.7), 2.25(3H, s), 2.09-2.01(1H, m), 1.77-1.70(1H, m) VIII-93

10.07(1H, bs), 8.74(1H, bs), 8.59(1H, s), 8.22(1H, d, J = 7.6 Hz),7.96(1H, d, J = 2.4 Hz), 7.80(1H, d, J = 8.8 Hz), 7.69(1H, dd, J = 2.4Hz, J = 8.8 Hz), 7.50-7.45(1H, m), 7.35-7 27(3H, m), 7.20-7.17(1H, m),5.27(2H, s), 4.40(2H, t, J = 5.6 Hz), 3.56(2H, t, J = 8.0 Hz), 2.85(2H,t, J = 8.4 Hz), 2.69(2H, t, J = 5.6 Hz), 2.25(3H, s), 1.04(6 H, d, J =5.6 Hz). VIII-94

10.07(1H, bs), 8.74(1H, bs), 8.59(1H, s), 8.22(1H, d, J = 8.8 Hz),7.97(1H, d, J = 2.4 Hz), 7.80(1H, d, J = 8.8 Hz), 7.72(1H, bs), 7.69(1H,dd, J = 2.4 Hz, J = 8.8 Hz), 7.50-7.45(1H, m), 7 35-7.27(3H, m),7.21-7.16(1H, m), 5.27(2H, s), 4.41(2H, t, J = 5.6 Hz), 3.17(2H, bs),3.10(2H, s), 2.80(2H, t, J = 5.6 Hz), 2.70(2H, t, J = 5.6 Hz), 2.26(3H,s). VIII-95

10.27(1H, brs), 8.74(1H, s), 8.58(1H, s), 8.23-8.21(1H, m), 7.95(1H, s),7.80(1H, d, J = 8.8), 7.69-7.67(1H, m), 7.50-7.44(1H, m), 7.34-7 26(2H,m), 7.20-7.16(1H, m), 5.27(2H, s), 4.39(2H, t, J = 5.6 Hz), 3.18(8 H,brs), 2.96(2H, t, J = 5 6 Hz), 2.55(3H, s) VIII-96

10.1(1H, s), 8.79(1H, s), 8.59(1H, s), 8.21(1H, d, J = 8 Hz), 7.96(1H,s), 7.79(1H, d, J = 8.8 Hz), 7.68(1H, d, J = 8.8 Hz), 7.44-7.50(1H, m),7 24-7.36(3H, m), 7.18(1H, t, J = 7.2 Hz), 5.27(2H, s), 4.87(2H, t, J =10 Hz), 3.29-3 34(2H, m), 2.70(2H, t, J = 6.4 Hz), 2.26-2.35(4H, m),2.25(3H, s), 2.14(3H, s) VIII-97

10.1(1H, s), 8.74(1H, s), 8.59(1H, s), 8.21(1H, d, J = 8.8 Hz), 7.96(1H,s), 7.80(1H, s), 7.69(1H, s), 7.42-7.50(1H, m), 7.13-7.36(4H, m),5.27(2H, s), 4.52(1H, s), 4.36(2H, brs), 3.40-3.50(1H, brs), 2.80(2H,brs), 2.69(2H, brs), 2.10-2.27(5 H, m), 1.69(2H, brs), 1.40(2H, brs)

TABLE 28 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-98 

8.74(1H, s), 8.58(1H, s), 8.21(1H, d, J = 9.2 Hz), 7.96(1H, s), 7.79(1H,d, J = 9.2 Hz), 7.68(1H, d, J = 9.2 Hz), 7.48(1H, dd, J = 5.8 Hz, J =7.2 Hz), 7.35-7.26(3H, m), 7.18(1H, t, J = 9.2 Hz), 5.27(2H, s),4.36(2H, t, J = 9.2 Hz), 3.38(1H, dd, J = 5.8 Hz, J = 7.2 Hz), 2.86(2H,d, J = 11.6 Hz), 2.68(2H, t, J = 6.0 Hz), 2.25(3H, s), 2.06(2H, t, J =11.2 Hz), 1.66(2H, d, J = 11.7 Hz), 1.09(2H, t, J = 7.2 Hz). VIII-99 

10.1(1H, bs), 8.78(1H, bs), 8.59(1H, s), 8.22(1H, d, J = 8.0 Hz),7.97(1H, s), 7.81(1H, d, J = 8.8 Hz), 7.70(1H, d, J = 6.4 Hz),7.49-7.45(1H, m), 5.27(2H, s), 4.49-4.12(2H, m), 3.41-3.38(1H, m), 282-2.65(2H, m), 2.25(3H, s), 1.79(3H, s), 1.09(2H, t, J = 7.2 Hz).VIII-100

10.07(1H, s), 8.74(1H, s), 8.59(1H, s), 8.21(1H, d, J = 9.2 Hz),8.59(1H, s), 8.21(1H, d, J = 9.2 Hz), 7.96(1H, s), 7.80(1H, d, J = 8.4Hz), 7.68(1H, d, J = 8.4 Hz), 7.50-7.45(1H, m), 7.35-7.27(3H, m),7.19(1H, t, J = 8.0 Hz), 7.04(1H, t, J = 6.0 Hz), 5.20(2H, s), 4.30(2H,bs), 3.10(1H, bs), 2.91(3H, s), 2.63(2H, d, J = 2.4 Hz), 2.55(3H, s),2.03-1.99(2H, m), 1.77(2H, d, J = 22.0 Hz), 1.48-1.38(2H, m), 1.24(2H,bs). VIII-101

10.09(1H, bs), 8.75(1H, s), 8.58(1H, s), 8.20(1H, d, J = 8.7 Hz),7.95(3H, d, J = 2.1 Hz), 7.80(1H, d, J = 8.7 Hz), 7.68(1H, d, J = 9.0Hz), 7.51-7.44(1H, m), 7.35-7.26(3H, m), 7 21-7.16(1H, m), 5.27(2H, s),4.20-4.09(2H, m), 3.79(1H, dd, J = 2.7 Hz, J = 10.8 Hz), 3.68-3.64(1H,m), 3.13-3.08(1H, m), 2.82-2.71(3H, m), 2.26(3H, s) VIII-102

10.11(1H, bs), 8.74(1H, s), 8.57(1H, s), 8.22-8.19(1H, m), 7.96(1H, m),7.80(1H, d, J = 9.0 Hz), 7.69-7.66(1H, m), 7.51-7.44(1H, m),7.35-7.26(3H, m), 7.21-7.16(1H, m), 5.27(2H, s), 4 20-4 09(2H, m),3.79(1H, dd, J = 3.0 Hz, J = 10.8.Hz), 3 68-3.64(1H, m), 3.25-3.18(1H,m), 3.13-3.05(1H, m), 2.82-2.71(2H, m), 2.26(3H, s). VIII-103

10.09(1H, brs), 8.74(1H, s), 8 59(1H, s), 8.21(1H, d, 9.0 Hz), 7.96(1H,s), 7.79(1H, d, J = 9.0 Hz) 7.68(1H, d, J = 9.0 Hz), 7.49-7.44(1H, m),7.34-7.22(3H, m), 7.19-7.15(1H, m), 5.27(2H, s), 4.11(2H, d, J = 4.8Hz), 2.95-2.50(6 H, m), 2.34-2.26(4H, m) VIII-104

10.07(1H, s), 8.75(1H, d, J = 1.8 Hz), 8.58(1H, s), 8.22(1H, dd, J = 1.8Hz, J = 9.0 Hz), 7.96(1H, d, J = 2.4 Hz), 7.79(1H, d, J = 8.7 Hz),7.68(1H, dd, J = 1.8 Hz, J = 9.3 Hz), 7.51-7.44(1H, m), 7.35-7.26(3H,m), 7.21-7.15(1H, m), 5.27(2H, s), 4.35(1H, dd, J = 2.7 Hz, J = 11 7Hz), 4.24(1H, dd, J = 3.9 Hz, J = 11.7 Hz), 4.12(1H, d, J = 17.4 Hz),3.90-3.76(3H, m), 3.50(1H, dt, J = 2.4 Hz, J = 11.1 Hz), 2.83-2 71(2H,m), 2.26(3H, s).

TABLE 29 Compound No R^(B) ¹H-NMR(d₆-DMSO) VIII-105

10 09(1H, brs), 8.73(1H, s), 8.58(1H, s), 8.20(1H, d, 7.8 Hz), 7.96(1H,s), 7.79(1H, d, J = 9.0 Hz), 7.69(1H, d, J = 8.4 Hz), 7.51-7.42(1H, m),7.35-7.25(3H, m), 7.22-7.16(1H, m), 5.27(2H, s), 4.31(2H, d, 4.5 Hz),2.95-2.53(5 H, m), 2.34-2.10(5 H, m) VIII-106

10 1(1H, s), 8.75(1H, s), 8.59(1H, s), 8.21(1H, d, J = 8.8 Hz), 7.97(1H,s), 7.80(1H, d, J = 8.4 Hz), 7.69(1H, d, J = 8.8 Hz), 7.43-7.52(1H, m),7.15-7.37(4H, m), 5.27(2H, s), 4.23-4.29(1H, m), 4.11-4.17(1H, m),3.69(1H, d, J =12 Hz), 3.37-3.45(1H, m), 3.23-3.32(1H, m), 2.66-2.80(3H,m), 2.28-2.40(1H, m), 2.26(3H, s), 1.16(3H, d, J = 6 Hz) VIII-107

10.1(1H, s), 8.75(1H, s), 8 59(1H, s), 8.21(1H, d, J = 8.8 Hz), 7.97(1H,s), 7.80(1H, d, J = 8 4 Hz), 7.69(1H, d, J = 8.8 Hz), 7.43-7.52(1H, m),7.15-7 37(4H, m), 5.27(2H, s), 4.23-4.29(1H, m), 4.11-4.17(1H, m),3.69(1H, d, J = 12 Hz), 3 37-3.45(1H, m), 3.23-3.32(1H, m),2.66-2.80(3H, m), 2.28-2.40(1H, m), 2.26(3H, s), 1.16(3H, d, J = 6 Hz)VIII-108

10.09(1H, brs), 8.75(1H, s), 8.59(1H, s), 8.21(1H, d, 10.5 Hz), 7.96(1H,s), 7.80(1H, d, J = 9.0 Hz), 7.68(1H, d, J = 9.0 Hz), 7.52-7.44(1H, m),7.35-7.25(3H, m), 7.22-7.16(1H, m), 5.27(2H, s), 4.44(1H, m), 4.18(1H,m), 2.80-2.60(4H, m), 2.32-2.00(12H, m) VIII-109

10.1(1H, s), 8.74(1H, s). 8.59(1H, s), 8.21(1H, d, J = 8.0 Hz), 7.96(1H,s), 7.80(1H, d, J = 8.8 Hz), 7.66-7.70(1H, m), 7.43-7.50(1H, m), 715-7.36(4H, m), 5.72(2H, s), 4.10-4.27(2H, m), 3.75-3.82(1H, m),3.45-3.55(1H, m), 2.85(1H, d, J = 10 Hz), 2 74(1H, d, J = 11 Hz),2.37(1H, t, J = 11 Hz), 2.26(4H, brs), 1.03(3H, d, J = 6.4 Hz). VIII-110

10.1(1H, s), 8.74(1H, s), 8.58(1H, s), 8.21(1H, d, J = 8.8 Hz), 7.96(1H,s), 7.80(1H, d, J = 8.4 Hz), 7.68(1H, s, J = 9.6 Hz), 7.42-7.52(1H, m),7.14-7.37(4H, m), 5.27(2H, s), 4.38-4.55(2H, m), 3.80-4.05(2H, m),2.75-2.85(2H, m), 2.65-2.72(1H, m), 2.30-2.40(1H, m), 2.26(3H, s),1.06(3H, d, J = 5 Hz) VIII-111

10.08(1H, s), 8.74(1H, s), 8.59(1H, s), 8.20(1H, d, J = 8.7 Hz),7.98(1H, d, J = 0.9 Hhz), 7.83-7.72(2H, m), 7.10(1H, dd, J = 2.7 Hz, J =9.0 Hz), 7.51-7.44(1H, m), 7.34-7.26(3H, m), 7.22-7.16(1H, m), 5.27(2H,s), 4.32(2H, m), 3.65(1H, m), 3.17(2H, s), 3.10-2.84(3H, m), 2.26(3H,s). VIII-112

(di-HCl salt) 12.03(1H, brs), 8.93(1H, s), 8.46(1H, d, J = 9.0 Hz),8.02(1H, d, J = 8.7 Hz), 7.92(1H, d, J = 2.4 Hz), 7.68-7.67(1H, m9,7.52-7.36(1H, m), 7.35-7.31(3H, m), 7.23-7.19(1H, m), 5.31(2H, s),4.58(2H, m), 4.33(1H, brs), 3.99-3.23(12H, m), 2.29(3H, s).

TABLE 30 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-113

10.09(1H, brs), 8.74(1H, s), 8.58(1H, s), 8.20(1H, d, J = 8.7 Hz),7.96(1H, d, J = 2.4 Hz), 7.79(1H, d, J = 8.7 Hz), 7.68(1H, dd, J = 2.7Hz, J = 9.0 Hz), 7.51-7.44(1H, m), 7.36-7.16(4H, m), 5.27(2H, s),4.15(2H, m), 3.07(1H, m), 2.87-2.55(4H, m), 2.26(3H, s), 2.15(3H, s),1.90(1H, m), 1.71(1H, m). VIII-114

(di-HCl salt) 11.65(1H, bs), 9.46-9.35(2 H m), 9.04(1H, s), 8.88(1H, s),7.95(1H, d, J = 9.0 Hz), 7.89(1H, d, J = 2.4 Hz), 7.66-7.62(1H, m),7.52-7.45(1H, m), 7.36-7.31(3H, m), 7.23-7.17(1H, m), 5.31(2H, s),4.35-4.34(2H, m), 4.24-4.21(1H, m), 4.04-3.98(1H, m), 3.85-3.77(1H, m),3.05-2.85(3H, m), 2.28(3H, s). VIII-115

VIII-116

10.1(1H, s), 8.74(1H, s), 8.59(1H, s), 8.21(1H, d, J = 8.0 Hz), 7.96(1H,s), 7.80(1H, d, J = 8.8 Hz), 7.66-7.70 (1H, m), 7 43-7 50(1H, m),7.15-7.36(4H, m), 5.72(2H, s), 4.10-4.27(2H, m), 3.75-3.82(1H, m), 345-3 55(1H, m), 2.85(1H, d, J = 10 Hz), 2.74(1H, d, J = 11 Hz), 2.37(1H,t, J = 11 Hz), 2.26(4H, brs), 1.03(3H, d, J = 6.4 Hz). VIII-117

10.1(1H, s), 8.74(1H, s), 8.58(1H, s), 8.21(1H, d, J = 8.8 Hz), 7.96(1H,s), 7.80(1H, d, J = 8.4 Hz), 7.68(1H, s, J = 9.6 Hz), 7.42-7.52(1H, m),7.14-7.37(4H, m), 5.27(2H, s), 4.38-4.55(2H, m), 3.80-4.05(2H, m),2.75-2.85(2H, m), 2.65-2.72(1H, m), 2.30-2.40(1H, m), 2.26(3H, s),1.06(3H, d, J = 5 Hz) VIII-118

10.10(1H, s), 8.76(1H, s), 8.59(1H, s), 8.22(1H, d, J = 8.7 Hz),7.96(1H, d, J = 2.1 Hz), 7.81(2H, d, J = 8.7 Hz), 7.69(1H, dd, J = 2 1Hz, J = 8.7 Hz), 7.44-7.52(1H, m), 7.27-7.35(2H, m), 7 16-7.22(1H, m),5.27(2H, s), 4.20-4.35(2H, m), 3 84-3.98(1H, m), 2.85-3.15(6 H, m),2.28(3H, m). VIII-119

(di-HCl salt) 9.14(1H, s), 8.91(1H, s), 8 61-8.55(1H, m), 8.41(1H, d, J= 9.0 Hz), 8.22(1H, d, J = 9.0 Hz), 8.00-7.97(1H, m), 7 91(1H, s),7.66(1H, d, J = 9.0 Hz), 7.52-7.45(1H, m), 7.37-7.30(3H, m),7.23-7.17(1H, m), 5.32(2H, s), 4.40(2H, m), 4.18(1H, m), 3 65-3.20(4H,m), 2.287(3H, s) VIII-120

10 1(1H, s), 8.71(1H, s), 8.59(1H, s), 8.16(1H, d, J = 8.8 Hz), 7.98(1H,s), 7.80(1H, d, J = 9 2 Hz), 7 69(1H, d, J = 9.2 Hz), 7.44-7.51(1H, m),7.14-7.36(4H, m), 5.27(2H, s), 4.31(2H, t, J = 5.6 Hz), 2.85(2H, t, J =5.6 Hz), 2.35(3H, s), 1.70-1.78(1H, m), 1.02-1.07(2H, m), 0.90-0 95(2H,m)

TABLE 31 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-121

10.1(1H, s), 8.82(1H, s), 8.61(1H, s), 8.27(1H, d, J = 7.6 Hz), 7.97(1H,s), 7.84(1H, d, J = 9.6 Hz), 7.70(1H, d, J = 7.6 Hz), 7.43-7.51(1H, m),7.25-7.36(3H, m), 7.15-7.22(1H, m), 5.62(1H, s), 5 72(2H, s),4.49-4.55(4H, m), 3.29-3.40(2H, m), 2.66(3 H s) VIII-122

10.05(1H, s), 8.76(1H, s), 8.60(1H, s), 8.20(1H, d, J = 9.2 Hz),7.97(1H, s), 7.82(1H, d, J = 8.8 Hz), 7.68(1H, d, J = 9.2 Hz),7.53-7.45(1H, m), 7.37-7.27(3H, m), 7.19(1H, t, J = 8.4 Hz), 5.63(1H, t,J = 5.2 Hz), 5.27(2H, s), 4.70(2H, d, J = 5.2 Hz), 4.40(2H, t, J = 6.0Hz), 2.81(2H, t, J = 6.0 Hz), 2.53(4H, bs), 1.68(4H, bs). VIII-123

10 02(1H, s), 8.89(1H, s), 8.60(1H, s), 8.22(1H, d, J = 9.3 Hz),8.00(1H, s), 7.83(1H, d, J = 8 7 Hz), 7.73(1H, d, J = 9 6 Hz), 7 51-744(1H, m), 7.35-7.29(2H, m), 7.22-7.16(1H, m), 5.2782H, s), 4 53(2H, s),3.40(5 H, bs), 2.51(5 H, bs). VIII-124

10.13(1H, s), 8.80(1H, s), 8.61(1H, s), 8.21(1H, d, J = 8.4 Hz), 799(1H, s), 7.83(1H, d, J = 8.8 Hz), 7.71(1H, d, J = 8.8 Hz),7.51-7.45(1H, m), 7.35-7 27(3H, m), 7.19(1H, t, J = 8.4 Hz), 5.27(2H,s), 4.53(2H, s), 4 46(2H, t, J = 5.6 Hz), 2.93(2H, bs), 2.65(4H, bs),1.72(4H, bs). VIII-125

10.09(1H, s), 8.76(1H, bs), 8.59(1H, s), 8 19(1H, d, J = 9.0 Hz),7.96(1H, bs), 7.82(1H, d, J = 8.7 Hz), 7.67(1H, bd, J = 7.5 Hz),7.51-7.44(1H, m), 7.35-7.26(3H, m), 7.21-7.16(1H, m), 5.27(2H, s),4.52(2H, s), 4.23(1H, dd, J = 5.7 Hz, J = 10.8 Hz), 4.17(1H, dd, J = 6.3Hz, J = 10.8 Hz), 3.79(1H, dd, J = 8.0 Hz, J = 10.8 Hz), 3.65(1H, bd, J= 7.8 Hz), 3.40(3H, s), 3.27-3.20(1H, m), 3.13-3.04(1H, m). VIII-126

10.10(1H, bs), 8.76(1H, d, J = 1.5 Hz), 8.59(1H, s), 8.19(1H, dd, J =1.8 Hz, J = 8.7 Hz), 7.96(1H, d, J = 2.1 Hz), 7.83(1H, d, J = 9.0 Hz),7.71-7.64(1H, m), 7.52-7.44(1H, m), 7.35-7 27(3H, m), 7.22-7.16(1H, m),5 27(2H, s), 4.53(2H, s), 4.23(1H, dd, J = 6.3 Hz, J = 11.4 Hz),4.17(1H, dd, J = 6.3 Hz, J = 10.8 Hz), 3.80(1H, dd, J = 3.0 Hz, J = 10.8Hz), 3.68-3.64(1H, m), 3.12-3 07(1H, m), 2.82-2.70(2H, m). VIII-127

10.1(1H, s), 8.76(1H, s), 8.59(1H, t, J = 5.6 Hz), 8.20(1H, d, J = 8.8Hz), 7.98(1H, s), 7.81(1H, d, J = 8.8 Hz), 7.70(1H, d, J = 8.8 Hz),7.44-7.51(1H, m), 7.15-7.37(4H, m), 5.27(2H, s), 4.34(2H, t, J = 6 Hz),2.86(2H, t, J = 5.6 Hz), 2.61(2H, t, J = 7.2 Hz), 2.36(3H, s), 1.67(2H,q, J = 7.2 Hz), 1.05(3H, t, J = 7.2 Hz)

TABLE 32 [Chemical formula 82] (VIII)

Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-128

10.0(1H, s), 8.74(1H, s), 8.60-8.58(2H, m), 8.21(1H, d, J = 8.8),7.96(1H, s), 7.90-7.86(1H, m), 7.79(1H, d, J = 8.8), 7.68-7 66(1H, m),7.58 (1H, d, J = 7.6), 7.38-7.35(1H, m), 7.27(1H, d, J = 8.8), 5.30(2H,s), 4.61-4 60(1H, m), 4.37-4.35 (2H, m), 3.52-3.38(1H, m), 2.93-2.92(1H,m), 2.76-2.66(2H, m), 2.24(3H, s), 2.00-1.95(1H, m), 1.89-1.84(1H, m),1.79-1.77(1H, m), 1.62-1.59 (1H, m), 1.45-1.36(1H, m), 1.10-1.02(1H, m).VIII-129

10.09(1H, s), 8.61-8.59(2H, m), 8.21(1H, d, J = 9.2 Hz), 8 07(1H, s),7.89(1H, d, J = 7.6 Hz), 7.80(1H, d, J = 8.4 Hz), 7 68(1H, d, J = 9.2Hz), 7.37(1H, t, J = 7.6 Hz), 7.28(1H, d, J = 8.8 Hz), 5.31(2H, s),4.60(2H, d J = 6.0 Hz), 2.27(3H, s), 0.89(3H, d, J = 7.6 Hz). VIII-130

(tri-HCl salt) 12.58(1H, s), 9.44(1H, s), 9.33(1H, bs), 9.09(1H, bs),8.95(1H, s), 8.78(1H, d, J = 4.4 Hz), 8.46(1H, d, J = 8.8 Hz), 8.23(1H,t, J = 6.8 Hz), 8.09(1H, d, J = 8.4 Hz), 7.94(1H, d, J = 2.4 Hz),7.86(1H, d, J = 8.0 Hz), 7.72-7.67(2H, m), 7.39(1H, d, J = 9.2 Hz),5.51(2H, s), 4.61(2H, bs), 3.61-3.47(5 H, m), 2.28(3H, s), 1.28(3H, d, J= 6.4 Hz). VIII-131

10.0(1H, s), 8 74(1H, s), 8.60-8.58(2H, m), 8.20(1 H d, J = 8.8),7.97(1H, s), 7.90-7.86(1H, m), 7.79(1H, d, J = 8.4), 7 69-7 67(1H, m),7.58(1H, d, J = 7.6), 7 38-7.35(1H, m), 7.27(1H, d, J = 9.2), 5.30(2H,s), 4.24 4.23(2H, m), 3.44-3.34(2H, m), 2.97-2.92(1H, m), 2.38(3H, s),2.26(3H, s). VIII-132

10.08(1H, s), 8.98(1H, s), 8.61-8.59(2H, m), 8.23(1H, d, J = 8.8 Hz),7.98(1H, s), 7.89(1H, t, J = 7.2 Hz), 7.80(1H, d, J = 8.8 Hz), 7 69(1H,d, J = 9.2 Hz), 7.59(1H, t, J = 8.0 Hz), 7.37(1H, d, J = 7.6 Hz),7.28(1H, d, J = 8.8 Hz), 5.31(2H, s), 4.33(2H, t J = 4.8 Hz), 3.26(2H,t, J = 6.4 Hz), 3.03(5 H, bs), 2.94(2H, bs), 2.26(3H, s). VIII-133

10.0(1H, s), 8.74(1H, s), 8.60-8.58(2H, m), 8.21(1H, d, J = 8.0),7.97(1H, m), 7.90-7.86(1H, m), 7.80(1H, d, J = 8.8), 7.69-7.67(1H, m),7.59(1H, d, J = 8.0), 7.38-7.35(1H, m), 7.28(1H, d, J = 9 2), 5.30(2H,s), 4.32-4.29(2H, m), 3.22-3.18(2H, m), 2.90-2.87(2H, m), 2.57-2.53(2H,m), 2.25(3H, s), 2.20-2.16(2H, m), 1.91-1.84(2H, m), 1.62-1.55(1H, m)VIII-134

10.11(1H, brs), 8.75(1H, s), 8.61-8.59(2H, m), 8.22(1H, d, J = 9.0 Hz),7.91-7 78(3H, m), 7.67(1H, d, J = 9.0 Hz), 7 59(1H, d, J = 7.8 Hz),7.40-7.36(1H, m), 7.29(1H, d, J = 9 0 Hz), 5.31(2H, s), 4.32(2H, m),3.13(2H, m), 2.93(2H, m), 2.66(2H, m), 2.26(3H, s), 1.78(3H, s)

TABLE 33 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-135

10.09(1H, brs), 8.75(1H, s), 8.61-8.59(2H, m), 8.22(1H, d, J = 9.0 Hz),7.97(1H, s), 7.92-7 86(1H, m), 7.81(1H, d, J = 9.0 Hz), 7.69(1H, d, J =9.0 Hz), 7.59(1H, d, J = 7.8 Hz), 7.40-7.36(1H, m), 7.29(1H, d, J = 9.0Hz), 6.47(2H, brs), 5.31(2H, s), 4.34(2H, m), 3.99(2H, m), 2.99(2H, m),2.84(2H, m), 2.26(3H, s) VIII-136

10.10(1H, brs), 8.75(1H, s), 8.61-8.59(2H, m), 8 22(1H, d, J = 9.0 Hz),7.97(1H, s), 7.92-7.86(1H, m), 7.81(1H, d, J = 9.0 Hz), 7.69(1H, d, J =9.0 Hz), 7 59(1H, d, J = 7.8 Hz), 7.40-7.36(1H, m), 7 29(1H, d, J = 9.0Hz), 5.31(2H, s), 4.33(2H, t, 6 0 Hz), 3.00(2H, t, 6.0 Hz), 2.25(3H, s),2.23(1H, m), 0.408(2H, m), 0.29(2H, m) VIII-137

(tri-HCl salt) 12.14(1H, brs), 9.28(1H, s), 8.93(1H, s), 8.64(1H, d, J =4.2 Hz), 8.44(1H, d, J = 10.5 Hz), 8.02-7.91(3H, m), 7.69-7.62(1H, m),7.46-7.42(1H, m), 7.37(1H, d, 9.0 Hz), 5.38(2H, s), 4.59(2H, m),4.19(1H, m), 3.81(1H, m), 3.71(1H, m), 3 47(2H, m), 3.21(1H, m),3.02(1H, m), 2.28(3H, s), 2.02(1H, m), 1.84(2H, m), 1.56(1H, m) VIII-138

(tri-HCl salt) 9.28(1H, s), 8.93(1H, s), 8.64(1H, d, J = 4.2 Hz),8.44(1H, d, J = 10.5 Hz), 8.02-7.91 (3H, m), 7.69-7.62(1H, m),7.46-7.42(1H, m), 7.37(1H, d, 9.0 Hz), 5.38(2H, s), 4.59(2H, m), 419(1H, m), 3.81(1H, m), 3.71(1H, m), 3.47(2H, m), 3.21(1H, m), 3.02(1H,m), 2.28(3H, s), 2.02(1H, m), 1.84(2H, m), 1.56(1H, m) VIII-139

10.08(1H, s), 8.75(1H, s), 8.61-8.58(2H, m), 8.22(1H, d J = 8.8 Hz),7.98(1H, s), 7.89(1H, t, J = 8.0 Hz), 7.68(1H, d, J = 8.4 Hz), 7.37(1H,t, J = 6.4 Hz), 7.37(1H, t, J = 6.4 Hz), 7.28(1H, d, J = 8.4 Hz),5.31(2H, s), 4.34(2H, t, J = 6.4 Hz), 3.33(1H, t, J = 6.4 Hz), 2.92(2H,t, J = 5.2 Hz), 2.65-2.61(1H, m), 2.26(3H, s), 1.75-1.70(1H, m),0.83(3H, d, J = 6.8 Hz). VIII-140

10 09(1H, s), 8.75(1H, s), 8.59(2H, bs), 8.22(1H, d, J = 8.8 Hz),7.98(1H, s), 7.89(1H, t, J = 6.4 Hz), 7.80(1H, d, J = 8.8 Hz), 7.69(1H,t, J = 8.4 Hz), 7.59 (1H, t, J = 8.4 Hz), 7.37(1H, d, J = 5.2 Hz),7.28(1H, d, J = 8.8 Hz), 5.31(2H, s), 4.34(2H, t, J = 6.4 Hz), 3.32(2H,t, J = 6.4 Hz), 2.92(2H, t, J = 5.6 Hz), 2.65-2.61(1H, m), 2.26(3H, s),1.75-1.68(1H, m), 1.24(1H, bs), 0.83(3H, d, J = 6.8 Hz). VIII-141

(tri-HCl salt) 12.48(1H, s), 9.48(1H, s), 9.42(1H, bs), 9.29(2H, bs),8.94(1H, s), 8 72(1H, s), 8.47 (1H, s), 8.13-8.06(1H, m), 7.92(1H, s), 776(1H, bs), 7.68(1H, bs), 7.59(1H, bs), 7.39(1H, bs), 5.46(2H, s),4.62(2H, bs), 3.88(4H, bs), 2.28(3H, s), 2.01-1.94(4H, m), 1.69-1.60(4H,m).

TABLE 34 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-142

10.07(1H, s), 8.74(1H, s), 8.59(2H, s), 8.20(1H, bs), 7.97(1H, s),7.89(1H, bs), 7.80(1H, d, J = 8.0 Hz), 7.68(1H, bs), 7.58(1H, d, J = 8.8Hz), 7.38(1H, bs), 7.28(1H, d, J = 9.2 Hz), 5.31(2H, s), 4.31(2H, bs),3.45(2H, bs), 2.94(2H, bs), 2.85-2.81(5 H, m), 2.26(3H, s), 1.89-185(2H, m), 1.36-1.28(2H, m) VIII-143

10.09(1H, brs), 8.74(1H, s), 8.61-8.59(2H, m), 8.22(1H, d, J = 9.0 Hz),7.97(1H, s), 7.92-7.86(1H, m), 7.81(1H, d, J = 9.0 Hz), 7.69(1H, d, J =9.0 Hz), 7.59(1H, d, J = 7.8 Hz), 7.40-7.36(1H, m), 7.29(1H, d, J = 9.0Hz), 5.31(2H, s), 4.23(2H, t, 5.4 Hz), 3 47(2H, t, 5.4 Hz)), 2.91(2H, t,5.4 Hz), 2 65(2H, m), 2.25(3H, s) VIII-144

(tri-HCl salt) 12.4(1H, s), 10.5(1H, s), 9.34(1H, s), 8.93(1H, s),8.68-8.67(1H, m), 8.45(1H, d, J = 9.2), 8.05-8.02(2H, m), 7.92-7.91(1H,m), 7.71-7.66(2H, m), 7.52-7.49(1H, m), 7.37(1H, d, J = 8.8), 5.41(2H,s), 4.73-4.67(1H, m), 3.30(6 H, s), 2.27(3H, s), 1.29-1.25(1H, m).VIII-145

10.08(1H, s), 8.75(1H, s), 8 59(2H, bs), 8.22(1H, d, J = 8.4 Hz),7.98(1H, bs), 7.89(1H, t, J = 8.0 Hz), 7.80(1H, d, J = 9.2 Hz), 7.68(1H,d, J = 8.8 Hz), 7.38(1H, d, J = 6.4 Hz), 7.28(1H, d, J = 8.8 Hz),5.31(2H, s), 4.36(4H, t, J = 6.4 Hz), 3.49(2H, bs), 2.79(2H, t, J = 6.0Hz), 2 30(3H, s), 2.25(3H, s). VIII-146

(tri-HCl salt) 12.70(1H, s), 10.83(1H, bs), 9.49(1H, s), 8.95(1H, s),8.77(1H, bs), 8.44(1H, d, J = 8.84 Hz), 8.23(1H, bs), 8.10(1H, d, J =8.8 Hz), 7.95(1H, s), 7.85(1H, d, J = 6.8 Hz), 7.74-7.68(2H, m),7.39(1H, d, J = 8.4 Hz), 5.51(2H, s), 4.70(2H, bs), 7 75-7 42(4H, m),3.48-3.44(1H, m), 3.40(1H, bs), 3.30(3H, s), 2.90(3H, s), 2.28(3H, s).VIII-147

10.28-10.03(1H, m), 8.75(1H, s), 8.61-8.58(2H, m), 8.21(1H, d, J = 8.8Hz), 7.98(1H, s), 7 89(1H, t, J = 8.0 Hz), 7.79(1H, d, J = 7 2 Hz),7.68(1H, d, J = 8.0 Hz), 7.37(3H, t, J = 6.0 Hz), 7.28(1H, t, J = 8.8Hz), 5.31(2H, s), 4.33(2H, t J = 6.4 Hz), 2.31(3H, s), 2.06(3H, s),1.88(2H, t, J = 6.4 Hz). VIII-148

10.09(1H, brs), 8.75(1H, s), 8.61-8.57(2H, m), 8.22(1H, d, J = 9.0 Hz),7.98(1H, s), 7.92-7.86(1H, m), 7.80(1H, d, J = 9.0 Hz), 7.68(1H, d, J =9.0 Hz), 7 59(1H, d, J = 7.8 Hz), 7.40-7.36(1H, m), 7.28(1H, d, J = 9.0Hz), 5.31(2H, s), 4.37(2H, m), 2.82(2H, m), 2.54(4H, m), 2.25(3H, s),1.69(4H, m)

TABLE 35 Compound No R^(B) ¹H-NMR(d₆-DMSO) VIII-149

10.09(1H, s), 8.75(1H, s), 8.70(2H, s), 8.20(1H, d, J = 8.0 Hz),8.07(2H, s), 7.98(1H, t, J = 4.8 Hz), 7.88(1H, t, J = 8.0 Hz), 7.68(1H,d, J = 8.0 Hz), 7.38(1H, s), 7.28(1H, d, J = 9.6 Hz), 5.31(2H, s),4.42(2H, s), 4.29-4.24(1H, m), 2.91-2.76(2H, m), 2.25(3H, s),2.17-2.12(1H, m), 1.75(3H, s), 1.53-1.34(1H, m), 1.11(2H, d, J = 4.4Hz). VIII-150

10.09(1H, s), 8.75(1H, s), 8.59(2H, s), 8.21(1H, bs), 7.98(1H, s),7.89(1H, s), 7.79(1H, s), 7.68(1H, s), 7.58(1H, s), 7.37(1H, s),7.28(1H, s), 5.31(2H, s), 4.36(2H, bs), 2.71(2H, bs), 2.25(3H, s),1.81(1H, bs), 1.66(2H, bs), 1.52(1H, bs), 1.24(2H, bs). VIII-151

10.09(1H, brs), 8.75(1H, s), 8.61-8.59(2H, m), 8.22(1H, d, J = 9.0 Hz),7.97(1H, s), 7.92-7.86(1H, m), 7.80(1H, d, J = 9.0 Hz), 7.69(1H, d, J =9.0 Hz), 7.59(1H, d, J = 7.8 Hz), 7.40-7.36(1H, m), 7.28 (1H, d, J = 9.0Hz), 6.48(2H, brs), 5.31(2H, s), 4.94 (1H, m), 4.37(2H, m),2.81-2.63(5H, m), 2.44 (1H, m), 2.25(3H, s), 2.14(1H, m), 1.69(1H, m)VIII-152

10.13(1H, brs), 8.79(1H, s), 8.61-8.58(2H, m), 8.23(1H, dd, J = 1.8 Hz,J = 8.7 Hz), 7.98(1H, d, J = 2.7 Hz), 7.92-7.86(1H, m), 8.80(1H, d, J =8.7 Hz), 7.79(1H, dd, J = 2.7 Hz, J = 9.0 Hz), 7.59(1H, d, J = 7.8 Hz),7.39-7.35(1H, m), 7.28(1H, d, J = 9.0 Hz), 5.31(2H, s), 4.91(1H, brs),4.36-4.24(3H, m), 3.59(1H, m), 2.99-2.812(2H, m), 2.26(3H, s), 2.13(1H,m), 1.50(1H, m). VIII-153

10.0(1H, br), 8.64(1H, s), 8.62-8.55(2H, m), 8.20(1H, d, J = 8.8),7.96(1H, s), 7.90-7.87(1H, m), 7.79(1H, d, J = 8.4), 7.68-7.66(1H, m),7.58(1H, d, J = 8.4), 7.38-7.35(1H, m), 7.27(1H, d, J = 8.8), 5.30(2H,s), 4.18-4.08(2H, m), 3.43-3.40(1H, m), 3.69(3H, s), 2.84-2.77(2H, m),2.25(3H, s), 1.88-1.55(3H, m), 1.50-1.38(1H, m). VIII-154

10.08(1H, br), 8.75(1H, s), 8.60-8.58(2H, m), 8.21-8.19(1H, m),7.98-7.97(1H, m), 7.93-7.86(1H, m), 7.79(1H, d, J = 8.8), 7.70-7.67(1H,m), 7.58(1H, d, J = 8.0), 7.38-7.35(1H, m), 7.27(1H, d, J = 9.2),5.30(2H, s), 4.30-4.20(2H, m), 3.01-2.96(1H, m), 2.68(1H, br), 2.41(3H,s), 2.24(3H, s), 1.99-1.89(1H, m), 1.73-1.66(2H, m), 1.62-1.53(1H, m).VIII-155

10.0(1H, brs), 8.73(1H, s), 8.50-8.58(2H, m), 8.31(1H, s), 8.22-8.20(1H,m), 7.96(1H, s), 7.90-7.86(1H, m), 7.79(1H, d, J = 8.8), 7.68-7.66(1H,m), 7.59(1H, d, J = 7.6), 7.38-7.35(1H, m), 7.28(1H, d, J = 9.2),5.30(2H, s), 4.93(1H, brs), 3.02(1H, d, J = 11.6), 2.24(3H, s),2.06-2.01(1H, m), 1.77-1.70(1H, m).

TABLE 36 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-156

10.13(1H, brs), 8.81(1H, s), 8.61-8.59(2H, m), 8.24(1H, d, J = 10.5 Hz),7.99(1H, s), 7.92-7.88(1H, m), 7.81(1H, d, J = 9.0 Hz), 7.70(1H, d, J =9.0 Hz), 7.59(1H, d, J = 7.8 Hz), 7.38-7.36(1H, m), 7.28(1H, d, J = 9.0Hz), 5.31(2H, s), 4.92(1H, s), 4.28(3H, m), 3.82(1H, m), 3.09(1H, d,11.4 Hz), 3.83(1H, d, 11.4 Hz), 2.27(3H, s), 1.87(1H, m), 1.65(1H, m)VIII-157

10.03(1H, br), 8.73(1H, s), 8.59-8.58(1H, m), 8.55(1H, s), 8.20(1H, d, J= 8.8), 7.94(1H, s), 7.89-7.85(1H, m), 7.78(1H, d, J = 8.4),7.66-7.64(1H, m), 7.57(1H, d, J = 7.6), 7.38-7.35(1H, m), 7.25(1H, d, J= 8.8), 5.28(2H, s), 4.20-4.08(2H, m), 2.85-2.74(2H, m), 2.24(3H, s),1.82-1.76(1H, m), 1.73-1.58(2H, m), 1.48-1.39(1H, m) VIII-158

10.07(1H, br), 8.74(1H, s), 8.60-8.58(2H, m), 8.22-8.19(1H, m),7.98-7.97(1H, m), 7.93-7.86(1H, m), 7.80(1H, d, J = 9.2), 7.70-7.67(1H,m), 7.59(1H, d, J = 7.6), 7.38-7.35(1H, m), 7.28(1H, d, J = 9.2),5.30(2H, s), 4.30-4.20(2H, m), 3.01-2.96(1H, m), 2.65(1H, br), 2.40(3H,s), 2.24(3H, s), 1.99-1.89 (1H, m), 1.78-1.66(2H, m), 1.62-1.53(1H, m).VIII-159

10.08(1H, s), 8.73(1H, s), 8.59-8.56(2H, m), 8.21-8.19(1H, m), 7.94(1H,s), 7.90-7.86(1H, m), 7.79(1H, d, J = 8.8), 7.66-7.64(1H, m), 7.58(1H,d, J = 7.6), 7.38-7.35(1H, m), 7.26(1H, d, J = 9.2), 5.29(2H, s),4.44(1H, brs), 4.25-4.21(1H, m), 4.15-4.11(1H, m), 3.05-2.96(2H, m),2.46-2.39(1H, m), 2.23(2H, s), 1.92-1.82(1H, m), 1.73-1.63(2H, m),1.59-1.54(1H, m). VIII-160

10.0(1H, s), 8.72(1H, s), 8.61-8.53(2H, m), 8.21-8.19(1H, m), 7.94(1H,s), 7.89-7.86(1H, m), 7.79(1H, d, J = 8.8), 7.66-7.64(1H, m), 7.58(1H,d, J = 8.0), 7.38-7.35(1H, m), 7.26(1H, d, J = 9.2), 5.29(2H, s),4.44(1H, brs), 4.25-4.21(1H, m), 4.15-4.11(1H, m), 3.05-2.96(2H, m),2.45-2.39(1H, m), 2.23(3H, s), 1.92-1.82(1H, m), 1.73-1.63(2H, m),1.60-1.53(2H, m). VIII-161

10.0(1H, brs), 8.73(1H, s), 8.60-8.57(2H, m), 8.21(1H, d, J = 8.4),7.95(1H, s), 7.90-7.86(1H, m), 7.79(1H, d, J = 8.8), 7.67-7.65(1H, m),7.58(1H, d, J = 7.6), 7.38-7.35(1H, m), 7.27(1H, d, J = 8.8), 5.30(2H,s), 4.93(1H, brs), 3.02(1H, d, J = 11.6), 2.24(3H, s), 2.06-2.01(1H, m),1.77-1.70(1H, m) VIII-162

10.07(1H, s), 8.75(1H, s), 8.61-8.59(2H, m), 8.23(1H, d, J = 8.8 Hz),7.98(1H, d, J = 2.4 Hz), 7.89(1H, t, J = 8.4 Hz), 7.80(1H, d, J = 8.8Hz), 7.68(1H, d, J = 6.4 Hz), 7.57(1H, t, J = 11.8 Hz), 7.28(1H, d, J =8.8 Hz), 5.31(2H, s), 4.40(2H, t J = 5.2 Hz), 3.32(4H, s), 3.09(4H, bs),2.96(2H, t, J = 5.6 Hz), 2.26(3H, s)

TABLE 37 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-163

10.07(1H, s), 8.75(1H, s), 8.59(2H, bs), 8.21(1H, d, J = 4.8 Hz),7.98(1H, s), 7.89(1H, t, J = 7.6 Hz), 7.80(1H, d, J = 8.4 Hz), 7.68(1H,d, J = 8.4 Hz), 7.60(1H, t, J = 8.4 Hz), 7.37(1H, t, J = 7.6 Hz),7.28(1H, d, J = 8.8 Hz), 5.31(2H, s), 4.40(2H, t J = 4.8 Hz), 3.60(4H,bs), 2.72(4H, t, J = 4.8 Hz), 2.25(3H, s). VIII-164

10.0(1H, s), 8.73(1H, s), 8.60-8.57(2H, m), 8.20(1H, d, J = 8.8),7.96(1H, s), 7.90-7.86(1H, m), 7.79(1H, d, J = 8.4), 7.67-7.65(1H, m),7.58(1H, d, J = 7.6), 7.38-7.35(1H, m), 7.27(1H, d, J = 8.8), 5.30(2H,s), 4.38-4.35(2H, m), 2.71-2.68(2H, m), 2.31(1H, br), 2.24(3H, s),2.13(3H, s). VIII-165

10.0(1H, s), 8.73(1H, s), 8.62-8.54(2H, m), 8.21-8.19(1H, m), 7.96(1H,s), 7.90-7.86(1H, m), 7.80-7.78(1H, m), 7.68-7.66(1H, m), 7.59(1H, d, J= 8.0), 7.38-7.36(1H, m), 7.27(1H, d, J = 8.8), 5.30(2H, s), 4.54(1H,brs), 4.37-4.34(2H, m), 2.83-2.75(2H, m), 2.69-2.66(2H, m), 2.24(3H, s),2.17-2.11(2H, m), 1.71-1.69(2H, m), 1.71-1.69(2H, m), 1.44-1.32(2H, m).VIII-166

10.08(1H, s), 8.75(1H, s), 8.59(2H, bs), 8.22(1H, d, J = 8.8 Hz),7.80(1H, s), 7.89(1H, t, J = 6.4 Hz), 7.80(1H, d, J = 8.4 Hz),7.70-7.67(1H, m), 7.59(1H, d, J = 8.4 Hz), 7.37(1H, bs), 7.28(1H, d, J =8.0 Hz), 5.31(2H, s), 4.41(2H, t, J = 4.4 Hz), 3.43(2H, bs), 2.76(2H,bs), 2.26(3H, s), 1.99(3H, s). VIII-167

10.10(1H, s), 8.73(1H, s), 8.60-8.56(2H, m), 8.20(1H, d, J = 8.8),7.94(1H, s), 7.90-7.86(1H, m), 7.79(1H, d, J = 8.8), 7.68-7.64(1H, m),7.58(1H, d, J = 7.6), 7.38-7.35(1H, m), 7.27(1H, d, J = 9.2), 5.29(2H,s), 4.20-4.08(2H, m), 3.79(1H, d, J = 10.4), 3.65(1H, d, J = 11.2),3.25-3.20(1H, m), 3.09(1H, br), 2.83-2.70(2H, m), 2.25(3H, s) VIII-168

10.0(1H, s), 8.73(1H, s), 8.59-8.57(2H, m), 8.19(1H, d, J = 8.8),7.95(1H, s), 7.89-7.85(1H, m), 7.78(1H, d, J = 8.8), 7.68-7.65(1H, m),7.58(1H, d, J = 7.6), 7.37-7.34(1H, m), 7.26(1H, d, J = 8.8), 5.29(2H,s), 4.26-4.14(2H, m), 3.75-3.72(2H, m), 2.85(1H, d, J = 12.4),2.69-2.61(2H, m), 2.45(1H, d, J = 10.8), 2.25(3H, s). VIII-169

10.0(1H, s), 8.74(1H, s), 8.60-8.58(2H, m), 8.20(1H, d, J = 8.8),7.96(1H, s), 7.90-7.86(1H, m), 7.80(1H, d, J = 8.8), 7.68-7.66(1H, m),7.59(1H, d, J = 7.6), 7.38-7.35(1H, m), 7.27(1H, d, J = 9.2), 5.30(2H,s), 4.20-4.08(2H, m), 3.79(1H, d, J = 10.4), 3.65(1H, d, J = 11.2),3.25-3.20(1H, m), 3.09(1H, br), 2.83-2.70(2H, m), 2.26(2H, s).

TABLE 38 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-170

10.09(1H, brs), 8.74(1H, s), 8.61-8.58(2H, m), 8.22(1H, d, J = 10.5 Hz),7.97(1H, s), 7.92-7.86(1H, m), 7.80(1H, d, J = 9.0 Hz), 7.68(1H, d, J =10.5 Hz), 7.59(1H, d, J = 8.1 Hz), 7.39-7.35(1H, m), 7.28(1H, d, J = 9.0Hz), 5.31(2H, s), 4.12(2H, d, 4.5 Hz), 2.95-2.53(5H, m), 2.34-2.09(5H,m) VIII-171

10.08(1H, brs), 8.74(1H, s), 8.61-8.59(2H, m), 8.21(1H, d, J = 9.0 Hz),7.98(1H, s), 7.92-7.86(1H, m), 7.81(1H, d, J = 9.0 Hz), 7.75(1H, s),7.67(1H, d, J = 9.0 Hz), 7.59(1H, d, J = 7.8 Hz), 7.40-7.36(1H, m),7.29(1H, d, J = 9.0 Hz), 5.31(2H, s), 4.31(2H, m), 3.66(1H, m),3.27-3.10(2H, m), 2.99-2.80(2H, m) VIII-172

10.09(1H, brs), 8.74(1H, s), 8.61-8.59(2H, m), 8.22(1H, d, J = 9.0 Hz),7.97(1H, s), 7.92-7.86(1H, m), 7.81(1H, d, J = 9.0 Hz), 7.68(1H, d, J =9.0 Hz), 7.59(1H, d, J = 7.8 Hz), 7.40-7.36(1H, m), 7.29(1H, d, J = 9.0Hz), 5.31(2H, s), 4.44(1H, m), 4.16(1H, m), 2.70-2.51(4H, m),2.30-2.16(10H, m), 2.09-1.88(2H, m) VIII-173

10.0(1H, br), 8.74(1H, s), 8.60-8.58(2H, m), 8.20(1H, d, J = 8.8),7.97(1H, s), 7.90-7.86(1H, m), 7.80(1H, d, J = 8.4), 7.68-7.66(1H, m),7.59(1H, d, J = 8.0), 7.38-7.35(1H, m), 7.28(1H, d, J = 9.2), 5.30(2H,s), 4.26-4.14(2H, m), 3.75-3.72(2H, m), 3.48-3.42(2H, m), 2.85(1H, d, J= 12.4), 2.69-2.60(2H, m), 2.45(1H, d, J = 10.4), 2.26(3H, s) VIII-174

(tri-HCl salt) 12.31(1H, brs), 9.41(1H, s), 8.97(1H, s), 8.73(1H, d, J =1.8 Hz), 8.49(1H, d, 8.7 Hz), 8.17-8.05(2H, m), 7.94(1H, s), 7.77(1H, d,J = 7.5 Hz), 7.69(1H, d, 8.7 Hz), 7.59(1H, t, J = 5.7 Hz), 7.38(1H, d, J= 8.7 Hz), 5.46(2H, s), 4.60(2H, m), 4.35-3.31(12H, m), 2.30(3H, s).VIII-175

VIII-176

(tri-HCl salt) 12.31(1H, brs), 9.41(1H, s), 8.97(1H, s), 8.73(1H, d, J =5.4 Hz), 8.49(1H, d, J = 8.7 Hz), 8.13(1H, s), 8.07(1H, d, J = 9.0 Hz),7.94(1H, s), 7.72(1H, d, J = 8.7 Hz), 7.02(1H, d, J = 9.0 Hz), 7.59(1H,s), 7.38(1H, d, J = 9.0 Hz), 5.46(2H, s), 4.65-3.62(10H, m), 2.89(3H,s), 2.30(3H, s).

TABLE 39 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-177

10.1(1H, s), 8.74(1H, s), 8.59(2H, brs), 8.21(1H, d, J = 8.8 Hz),7.97(1H, s), 7.85-7.92(1H, m), 7.80(1H, d, J = 8.4 Hz), 7.67(1H, d, J =9.6 Hz), 7.59(1H, d, J = 6.4 Hz), 7.34-7.40(1H, m), 7.29(1H, d, J = 8.8Hz), 5.31(2H, m), 4.10-4.35(2H, m), 3.75-3.82(1H, m), 3.48(1H, m),2.85(1H, d, J = 12 Hz), 2.74(1H, d, J = 13 Hz), 2.34-2.41(1H, m),2.26(4H, brs), 1.03(3H, d, J = 6.0 Hz) VIII-178

10.1(1H, s), 8.74(1H, s), 8.59(2H, brs), 8.21(1H, d, J = 8.8 Hz),7.97(1H, s), 7.79-7.93(2H, m), 7.66-7.70(1H, m), 7.59(1H, d, J = 6.4Hz), 7.38(1H, brs), 7.29(1H, d, J =8.8 Hz), 5.31(2H, m), 4.37-4.56(2H,m), 3.95-4.02(1H, m), 3.80-3.88(1H, m), 2.62-2.85(3H, m), 2.31-2.4(1H,m), 2.26(3H, s), 1.06(3H, d, J = 5.2 Hz) VIII-179

10.06(1H, brs), 8.75(1H, s), 8.61-8.59(2H, m), 8.22(1H, d, J = 9.0 Hz),7.97(1H, s), 7.92-7.86(1H, m), 7.81(1H, d, J = 9.0 Hz), 7.76(1H, s),7.69(1H, d, J = 9.0 Hz), 7.59(1H, d, J = 7.8 Hz), 7.40-7.36(1H, m),7.29(1H, d, J = 9.0 Hz), 5.31(2H, s), 4.30(2H, m), 3.65(1H, m), 3.16(2H,m), 2.99-2.80(2H, m), 2.26(3H, s) VIII-180

10.0(1H, brs), 8.76(1H, s), 8.60-8.58(2H, m), 8.19(1H, d, J = 8.8),7.97(1H, s), 7.89-7.86(1H, m), 7.81(1H, d, J = 8.8), 7.68-7.66(1H, m),7.58(1H, d, J = 7.6), 7.38-7.35(1H, m), 7.27(1H, d, J = 8.8), 5.30(2H,s), 4.51(2H, s), 4.38-4.35(2H, m), 3.40(3H, s), 2.87-2.84(2H, m),2.34(3H, s) VIII-181

10.0(1H, s), 8.76(1H, s), 8.59(2H, s), 8.19(1H, d, J = 8.8), 7.97(1H,s), 7.90-7.86(1H, m), 7.82(1H, d, J = 8.8), 7.69-7.66(1H, m), 7.59(1H,d, J = 8.0), 7.38-7.35(1H, m), 7.28(1H, d, J = 8.8), 5.30(2H, s),4.52(2H, s), 4.25-4.15(2H, m), 3.82-3.79(1H, m), 3.67-3.64(1H, m),3.40(3H, s), 3.26-3.21(2H, m), 3.14-3.05(1H, m), 2.81-2.72(2H, m)VIII-182

10.1(1H, s), 8.79(1H, s), 8.60(2H, s), 8.25(1H, d, J = 7.6 Hz), 7.98(1H,s), 7.89(1H, bs), 7.81(1H, d, J = 7.6 Hz), 7.69(1H, d, J = 7.6 Hz),7.60(1H, d, J = 7.2 Hz), 7.38(1H, bs), 7.29(1H, d, J = 8.4 Hz), 5.31(2H,s), 4.43(2H, bs), 3.14(2H, bs), 2.52(3H, s), 2.27(3H, s)

TABLE 40 [Chemical formula 83] (VIII)

Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-183

10.19(1H, s), 8.78(1H, s), 8.53(1H, s), 8.23(1H, dd, J = 8.4 Hz, J = 4.0Hz), 8.17(1H, s), 8.14(1H, s), 7.80-7.65(3H, m), 7.40-7.35(1H, m),7.13-7.04(3H, m), 5.72(2H, s), 4.32(2H, t, J = 6.0 Hz), 2.86(2H, t, J =6.0 Hz), 2.35(3H, s), 2.25(3H, s). VIII-184

(di-HCl salt) 12.46(1H, s), 9.37(1H, s), 8.87(1H, s), 8.48(1H, d, J =8.7 Hz), 8.27(1H, t, J = 5.4 Hz), 8.24(1H, s), 8.03(2H, m), 7.85(1H, d,J = 9.0 Hz), 7.68(1H, d, 9.0 Hz), 7.35(1H, s), 7.13-7.05(3H, m),5.75(2H, s), 4.58(2H, m), 7.13-7.05(3H, m), 5.75(2H, s), 4.58(2H, m),3.51-3.37(4H, m), 3.11(2H, m), 2.27(3H, s), 1.01(1H, s). VIII-185

(di-HCl salt) 10.12(1Hs), 8.82(1H, d, J = 1.5 Hz), 8.52(1H, s), 8.22(1H,dd, J = 1.8 Hz, J = 8.7 Hz), 8.14(1H, s), 7.80(1H, s), 7.80(1H, s),7.77-7.68(3H, m), 7.40-7.33(1H, m), 7.12-7.04(3H, m), 5.71(2H, s),4.86(1H, brs), 4.28(3H, m), 3.58(1H, m), 2.95-2.78(2H, m), 2.25(3H, s),2.11(1H, m), 1.47(1H, m). VIII-186

10.18(1H, s), 8.78(1H, s), 8.52(1H, s), 8.23-8.12(3H, m), 7.79-7.65(3H,m), 7.41-7.32(1H, m), 7.18(7.02)(3H, m), 5.71 (2H, s), 4.31(2H, m),3.14(2H, m), 2.29(2H, m), 2.87(3H, s) 2.77(6H, m), 2.24(3H, s). VIII-187

10.19(1Hs), 8.78(1H, s), 8.52(1H, s), 8.23-8.12(3H, m), 7.80-7.65(3H,m), 7.38-7.33(1H, m), 7.13-7.03(3H, m), 6.49(2H, brs), 5.71(2H, s),4.31(2H, m), 4.04-3.95(2H, m), 2.92(2H, m), 2.78(2H, m), 2.25(3H, s).VIII-188

(di-HCl salt) 12.09(1H, s), 8.96(1H, s), 8.83 (1H, s), 8.43(1H, d, J =8.7 Hz), 8.06(1H, s), 7.97(1H, d, J = 8.4 Hz), 7.83(1H, d, J = 9.0 Hz),7.67(1H, d, J = 1.8 Hz), 7.65(1H, dd, J = 2.1 Hz, J = 9.0 Hz),7.41-7.34(1H, m), 7.14-7.05(3H, m), 5.71(2H, s), 4.54(2H, m), 4.19(1H,m), 3.83-3.70(2H, m), 3.68-2.95(5H, m), 2.27(3H, s), 2.04(1H, m),1.93(1H, m), 1.56(1H, m). VIII-189

(di-HCl salt) 12.21(1H, brs), 8.97(1H, brs), 8.84(1H, s), 8.43(1H, dd, J= 1.5 Hz, J = 9.0 Hz), 8.07(1H, s), 8.01(1H, s), 7.99(1H, d, J = 9.0Hz), 7.84(1H, d, J = 9.0 Hz), 7.67(1H, dd, J = 1.8 Hz, J = 9.0 Hz),7.41-7.32(1H, m), 7.14-7.05(3H, m), 5.74(2H, s), 4.59(2H, m), 4.21(1H,m), 3.82-3.65(2H, m), 3.62-3.05(8H, m), 2.28(3H, s), 2.02(1H, m),1.83(1H, M), 1.55(1H, m).

TABLE 41 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-190

(di-HCl salt) 12.18(1H, s), 9.29(1H, s), 8.45(1H, dd, J = 1.2, J = 9.0Hz), 8.23(1H, s), 8.06(1H, s), 8.06(1H, d, J = 1.2 Hz), 7.99(1H, d, J =8.7 Hz), 7.87-7.82(1H, m), 7.67(1H, dd, J = 1.2 Hz, J = 9.0 Hz),7.39-7.14(1H, m), 7.14-7.05(3H, m), 5.74(2H, s), 4.61(2H(, m), 3.95(1H,m), 8.23(2H, m), 3.13(3H, m), 2.28(3H,s), 2.17(1H, m), 1.78(1H, m).VIII-191

(di-HCl salt) 12.18(1H, s), 9.12(1H, s), 8.87(1H, s), 8.46(1H, d, J =8.7 Hz), 8.43(1H, s), 8.23(1H, s), 8.04-7.97(2H, m), 7.87-7.82(1H, m),7.64(1H, dd, J = 1.2 Hz, J = 9.0 Hz), 7.37-7.14(1H, m), 7.11-7.05(3H,m), 5.74(2H, s), 4.61(2H(, m), 4.09-3.26(7H, m), 2.26(3H, s), 2.17(1H,m), 1.79(1H, s). VIII-192

10.17(1H, s), 8.78(1H, s), 8.51(1H, s), 8.20(1H, dd, J = 1.8 Hz, J = 8.7Hz), 8.14(1H, s), 7.80-7.65(3H, m), 7.40-7.33(1H, m), 7.13-7.03(3H, m),5.71(2H, s), 4.31(2H, t, J = 5.7 Hz), 3.41(2H, t, J = 6.3 Hz), 3.22(3H,s), 2.85(2H, m), 2.70-2.57(4H, m), 2.23(3H, s), 0.99(2H, t, J = 7.2 Hz).VIII-193

10.19(1H, s), 8.78(1H, s), 8.52(1H, s), 8.21(1H, d, J = 8.4 Hz),8.16(1H, s), 8.13(1H, s), 7.78-7.65(3H, m), 7.49-7.33(1H, m),7.13-7.04(3H, m), 6.48(2H, brs), 5.71(2H, s), 4.93(1H, m), 4.36(2H, t, J= 5.7 Hz), 2.80(3H, m), 2.71(2H, m), 2.42(1H, m), 2.24(3H, s), 2.10(1b,m), 1.66(1H, m). VIII-194

10.21(1H, s), 8.82(1H, d, J = 1.5 Hz), 8.52(1H, s), 8.22(1H, dd, J = 1.8Hz, J = 8.7 Hz), 8.14(1H, s), 7.80(1H, s), 7.77-7.66(3H, m),7.40-7.33(1H, m), 7.12-7.04(3H, m), 5.71(2H, s), 4.86(1H, brs), 4.28(3H,m), 3.58(1H, m), 2.95-2.78(2H, m), 2.25(3H, s), 2.11(1H, m), 1.47(1H,m). VIII-195

10.17(1H, s), 8.78(1H, d, J = 1.8 Hz), 8.52(1H, s), 8.19(1H, dd, J = 1.8Hz, J = 10.5 Hz), 8.13(1H, s), 7.80(1H, s), 7.77-7.33(1H, m),7.12-7.03(3H, m), 5.71(2H, s), 439(2H, t, J = 5.7 Hz), 3.58(4H, t, J =4.8 Hz), 2.71(2H, t, J = 6.0 Hz),, 2.50(2H, m), 2.24(3H, s). VIII-196

10.19(1H, s), 8.78(1H, d, J = 1.5 Hz), 8.19(1H, dd, J = 1.8 Hz, J = 10.5Hz), 8.16(1H, s), 8.13(1H, d, J = 1.5 Hz), 7.80(1H, s), 7.80-7.66(4H,m), 7.40-7.33(1H, m), 7.13-7.06(3H, m), 5.71(2H, s), 4.41(2H, t, J = 5.2Hz), 3.16(2H, m), 3.10(2H, s), 2.80(1H, t, J = 5.7 Hz), 2.67(3H, s),2.25(3H, s)

TABLE 42 Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-197

10.21(1H, s), 8.79(1H, d, J = 1.8 Hz), 8.53(1H, s), 8.21(1H, dd, J = 1.8Hz, J = 8.7 Hz), 8.17(1H, s), 8.13(1H, d, J = 1.5 Hz), 7.79(1H, d, J =13.2 Hz), 7.76(1H, d, J = 13.2 Hz), 7.67(1H, dd, J = 1.8 Hz, J = 9.0Hz), 7.41-7.34(1H, m), 7.16-7.04(3H, m), 5.72(2H, s), 4.20-4.09(2H, m),3.79(1H, dd, J = 2.7 Hz, J = 10.8 Hz), 3.68-3.64(1H, m), 3.30-3.19(1H,m), 3.13-3.10(1H, m), 2.78-2.74(3H, m), 2.26(3H, s). VIII-198

10.20(1H, brs), 8.79(1H, s), 8.53(1H, s), 8.22-8.13(3H, m),7.81-7.66(3H, m), 7.41-7.33(1H, m) 7.13-7.04(3H, m), 5.72(2H, s),4.13(2H, d, J = 5.2 Hz), 3.00-2.51(6H, m), 2.39-2.26(4H, m) VIII-199

(di-HCl salt) 12.69(1Hbrs), 9.44(1H, s), 8.69(1H, s), 8.47(1H, d, J =8.1 Hz), 8.23 (1H, d, J = 2.1 Hz), 7.38(1H, s), 7.19-7.01(1H, m),5.74(2H, s), 4.64(5H, m), 4.01(1H, m), 3.39-3.21(4H, m), 2.59(3H, s).VIII-200

10.19(1H, s), 8.81(1H, s), 8.53(1H, s), 8.21-8.14(3H, m),7.82(7.82-7.65(3H, m), 7.41(1H, m), 7.15-7.04(13H, m), 5.71(2H, s),4.68(1H, brs), 4.51(2H, s), 4.27(2H, m), 4.18(1H, m), 3.42(2H, m),3.45(3H, s), 2.87(1H, m), 2.69(1H, m), 2.04(1H, m), 1.41(1H, m).

TABLE 43 [Chemical formula 84] (VIII)

Compound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-205

10.43-10.40(1H, m), 8.79(1H, s), 8.70(1H, s), 8.25(1H, d, J = 8.4 Hz),8.11(2H, bs), 7.98-7.96(4H, m), 7.85(1H, d, J = 7.2 Hz), 7.69-7.62(3H,m), 4.24-4.20(2H, m), 3.28(3H, s), 2.94(1H, t, J = 6.4 Hz), 2.38(3H, s),2.25(3H, s). VIII-206

10.44(1H, bs), 8.78(1H, d, J = 1.5 Hz), 8.67(1H, bs), 8.24(1H, d, J =9.0 Hz), 8.16-8.05(2H, m), 7.99-7.94(4H, m), 7.84(1H, d, J = 8.7 Hz),7.71-7.60(3H, m), 4.24(1H, dd, J = 6.3 Hz, J = 11.7 Hz), 4.16(1H, dd, J= 4.8 Hz, J = 11.7 Hz), 3.75-3.71(2H, m), 3.51-3.37(1H, m), 2.84(1H, dd,J = 2.4 Hz, J = 12.3 Hz), 2.73-2.58(2H, m), 2.50-2.42(1H, m), 2.25(3H,s). VIII-207

10.45(1H, bs), 8.78(1H, d, J = 1.5 Hz), 8.67(1H, bs), 8.24(1H, dd, J =1.5 Hz, J = 8.7 Hz), 8.12-8.09(2H, m), 7.99-7.95(4H, m), 7.85(1H, d, J =8.7 Hz), 7.71-7.61(3H, m), 4.18(1H, dd, J = 6.0 Hz, J = 11.1 Hz),4.12(1H, dd, J = 6.3 Hz, J = 11.1 Hz), 3.78(1H, dd, J = 2.7 Hz, J = 1.5Hz), 3.65(1H, dt, J = 11.1 Hz, J = 2.7 Hz), 3.11-3.07(1H, m),2.81-2.69(3H, m), 2.25(3H, s). VIII-208

10.42(1H, s), 8.84(1H, s), 8.69(1H, s), 8.25(1H, d, J = 8.8 Hz),8.13(1H, d, J = 8.4 Hz), 8.00-7.97(3H, m), 7.87(1H, d, J = 8.8 Hz),7.97-7.62(5H, m), 4.51(2H, s), 4.42(2H, t, J = 5.2 Hz), 3.37(3H, s),2.97(2H, t, J = 4.8 Hz), 2.41(3H, s) VIII-209

10.45(1H, bs), 8.80(1H, bs) ,8.68(1H, bs), 8.23(1H, d, J = 7.5 Hz),8.14-8.06(2H, m), 7.99-7.95(4H, m), 7.87(1H, d, J = 9.0 Hz),7.69-7.60(3H, m), 4.52(2H, s), 4.23(1H, dd, J = 6.3 Hz, J = 10.8 Hz),4.17(1H, dd, J = 6.3 Hz, J = 10.8 Hz), 3.80(1H, dd, J = 2.7 Hz, J = 11.1Hz), 3.67-3.64(1H, m), 3.40(3H, s), 3.12-3.07(1H, m).

TABLE 44 [Chemical formula 85] (VIII)

Compound No. R^(C) ¹H-NMR(d₆-DMSO) VIII-210

10.13(1H, s), 8.82(1H, s), 8.60(1H, s), 8.26(1H, d, J = 9.2 Hz),8.18(1H, s), 7.82(1H, d, J = 8.8 Hz), 7.74(1H, s), 7.64(1H, d, J = 9.2Hz), 7.27-7.22(2H, m), 6.99(1H, d, J = 8.4 Hz), 4.50(2H, t, J = 5.2 Hz),2.64(3H, s), 2.50(2H, bs), 2.45(3H, s), 2.28(3H, s), 2.23(3H, s).VIII-211

10.26(1H, brs), 8.80(1H, s), 8.66(1H, s), 8.26-8.23(1H, m), 8.14(1H, s),7.88-7.79(2H, m), 7.62(1H, d, J = 8.4), 7.34(1H, dd, J = 8.4, 15.2),6.95-6.88(1H, m), 6.82-6.78(1H, m), 5.16(2H, s), 4.35(2H, t, J = 6.0Hz), 2.92(2H, t, J = 6.0 Hz), 2.38(3H, s), 2.26(3H, s), 2.26(3H, s).VIII-212

10.0(1H, brs), 8.74(1H, s), 8.62-8.58(3H, m), 8.21(1H, d, J = 8.8),7.97(1H, s), 7.80(1H, d, J = 8.8), 7.69-7.67(1H, m), 7.48-7.47(2H, m),7.25(1H, d, J = 9.2), 5.32(2H, s), 4.34-4.31(2H, s), 2.89-2.86(2H, m),2.36(3H, s), 2.25(3H, s). VIII-213

10.43(1H, s), 9.23(1H, s), 9.21(1H, s), 8.64(1H, s), 8.26(1H, d, J = 6.6Hz), 7.93(2H, d, J = 3.9 Hz), 7.84(1H, d, J = 6.9 Hz), 7.45(2H, d, J =5.7 Hz), 7.35(1H, d, J = 5.4 Hz), 7.27(2H, t, J = 5.7 Hz), 4.56(2H, d, J= 3.9 Hz), 2.64(3H, s), 2.28(3H, s), 1.99(3H, s). VIII-214

8.85(1H, s), 8.80(1H, s), 8.26(1H, d, J = 6.6 Hz), 8.12(1H, d, J = 6.3Hz), 7.99-7.96(4H, m), 7.85(1H, d, J = 6.6 Hz), 7.71-7.62(3H, m),4.33(2H, t, J = 4.2 Hz), 2.86(2H, t, J = 4.5 Hz), 2.35(3H, s), 2.25(3H,s). VIII-215

10.15(1H, s), 8.77(1H, s), 8.55(1H, s), 8.47(1H, s), 8.24(1H, d, J = 9.2Hz), 8.07(1H, d, J = 9.2 Hz), 7.81(1H, d, J = 9.2 Hz), 7.47-7.39(1H, m),7.32-7.28(2H, m), 7.16(1H, t, J = 7.6 Hz), 7.00(1H, d, J = 8.8 Hz),5.41(1H, s), 4.41(2H, t, J = 5.6 Hz), 3.10(2H, t, J = 5.2 Hz), 2.49(3H,s), 2.26(3H, s). VIII-216

10.3(1H, s), 8.84(1H, s), 8.72(1H, s), 8.42-8.65(2H, m), 8.26(1H, d, J =7.6 Hz), 7.98(1H, s), 7.91(1H, brs), 7.81(1H, brs), 7.71(1H, brs),7.47(1H, brs), 7.34(1H, d, J = 8.0 Hz), 5.30(2H, s), 4.53(2H, brs),3.38(2H, brs), 2.68(3H, s), 2.26(3H, s).

TABLE 45 Compound No. R^(C) ¹H-NMR(d₆-DMSO) VIII-217

10.1(1H, s), 8.76(1H, s), 8.59(1H, s), 8.57(1H, s), 8.24(1H, d, J = 10Hz), 7.94(1H, bs), 7.67-7.73(3H, m), 7.29-7.35(2H, m), 5.24(2H, s),4.40(2H, t, J = 5.6 Hz), 3.06(2H, t, J = 5.2 Hz), 2.49(3H, s), 2.48(3H,s), 2.26(3H, s)

TABLE 46 [Chemical formula 86] (VIII)

Comopund No. * R^(C) ¹H-NMR(d₆-DMSO) VIII-218 S

(tri-HCl salt) 12.18(1H, bs), 9.78(1H, m), 9.61(1H, m), 9.36(1H, s),8.94(1H, s), 8.48(1H, dd, J = 1.8 Hz, J = 9.0 Hz), 8.41(1H, d, J = 3Hz), 8.03(1H, d, J = 9 Hz), 7.76-7.73(2H, m), 7.64-7.60(2H, m), 7.13(1H,d, J = 8.7 Hz), 4.51-4.49(2H, m), 2.60(3H, s), 2.29(3H, s), 2.27(3H, s).VIII-219 R

10.46(1H, bs), 8.78(1H, d, J = 1.5 Hz), 8.67(1H, s), 8.24(1H, dd, J =1.5 Hz, J = 8.7 Hz), 8.12-8.09(2H, m), 7.99-7.95(4H, m), 7.85(1H, d, J =8.7 Hz), 7.71-7.60(3H, m), 4.17(1H, dd, J = 5.7 Hz, J = 11.1 Hz),4.12(1H, dd, J = 6.3 Hz, J = 11.1 Hz), 3.78(1H, dd, J = 2.7 Hz, J = 10.5Hz), 3.65(1H, dt, J = 10.8 Hz, J = 2.7 Hz), 3.26-3.18(1H, m),3.13-3.05(1H, m), 2.82-2.70(2H, m), 2.25(3H, s). VIII-220 S

10.26(1H, bs), 8.79(1H, s), 8.67(1H, s), 8.23(1H, d, J = 8.8 Hz),8.14(1H, s), 7.64(1H, d, J = 8.8 Hz), 7.62(1H, d, J = 8.8 Hz), 7.35(1H,dd, J = 8.0, J = 15.6), 6.96-6.86(2H, m), 6.82-6.78(1H, m), 5.16(2H, s),4.20-4.11(2H, m), 3.79(1H, d, J = 10.8 Hz), 3.66(1H, d, J = 11.2 Hz),3.22(2H, t, d = 10.4), 3.10-3.02(1H, m), 2.81-2.68(2H, m), 2.26(3H, s).VIII-221 R

10.26(1H, bs), 8.79(1H, s), 8.67(1H, s), 8.23(1H, d, J = 9.6 Hz),8.14(1H, s), 7.85-7.83(1H, m), 7.62(1H, d, J = 8.8 Hz), 7.35(1H, dd, J =8.0, J = 15.6), 6.95-6.88(2H, m), 6.82-6.78(1H, m), 5.16(2H, s),4.20-4.11(2H, m), 3.79(1H, d, J = 10.8 Hz), 3.66(1H, d, J = 11.2 Hz),3.22(2H, t, d = 10.4), 3.10-3.02(1H, m), 2.81-2.68(2H, m), 2.26(3H, s)(wherein an atom marked with * is an asymmetric carbon atom)

Example 11

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(carboxymethoxyimino)-2-butyn-1-yl)quinazoline(VIII-38)

4-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(methoxycarbonylmethoxyimino)-2-butyn-1-yl)quinazoline(VIII-43, 1.2 g) was dissolved in a mixture of 12 ml of tetrahydrofuranand 12 ml of methanol, and 1.5 ml of 2 mol/L aqueous sodium hydroxidesolution was added, followed by stirring at room temperature for 1.5hours. The reaction mixture was diluted with 20 ml of ethyl acetate, 1.6ml of 2 mol/L hydrochloric acid was added, and water was added, thereby,an objective substance was precipitated. A precipitate was collected byfiltration, washed with water and ethyl acetate, and dried to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(carboxymethoxyimino)-2-butyn-1-yl)quinazoline(VIII-38, 0.9 g) as a yellow solid.

¹H NMR (d₆-DMSO, δ): 10.18 (1H, brs), 8.77 (1H, s), 8.60 (1H, s), 8.19(1H, dd, J=2.0, 11.6 Hz), 7.95 (1H, d, J=3.2 Hz), 7.80 (1H, d, J=11.6Hz), 7.67 (1H, dd, J=3.2, 11.6 Hz), 7.51-7.44 (1H, m), 7.35-7.26 (3H,m), 7.22-7.15 (1H, m), 5.27 (2H, s), 4.83 (2H, s), 2.27 (3H, s).

(Step 2) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-((2-dimethylaminoethylcarbamoyl)methoxyimino)-2-butyn-1-yl)quinazoline(VIII-39)

4-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(carboxymethoxyimino)-2-butyn-1-yl)quinazoline(VIII-38, 70 mg), 24 mg of 1-hydroxybenzotriazole, and 27 mg of 1-ethyl3-(3-dimethylaminopropyl)carbodiimide hydrochloride were dissolved in1.4 ml of N,N-dimethylformamide, this was stirred at room temperaturefor 5 minutes, and 22 μl of N,N-dimethylethylenediamine was added,followed by stirring at room temperature for 2 hours. After completionof the reaction, the reaction mixture was diluted with ethyl acetate,and water and aqueous saturated sodium bicarbonate solution were addedto separate layers. The organic layer was washed with water, and driedover sodium sulfate, and the filtrate was concentrated. Ethyl acetatewas added to the concentrated residue to solidify the material, and thesolid was collected by filtration, and dried to obtain4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-((2-dimethylaminoethylcarbamoyl)methoxyimino)-2-butyn-1-yl)quinazoline(VIII-39, 30 mg) as a colorless crystal.

¹H NMR (d₆-DMSO, δ): 10.12 (1H, s), 8.77 (1H, s), 8.59 (1H, s), 8.19(1H, dd, J=2.0, 12.0 Hz), 8.08 (1H, brs), 7.95 (1H, d, J=3.2 Hz), 7.80(1H, d, J=11.6 Hz), 7.70-7.62 (2H, m), 7.51-7.44 (1H, m), 7.34-7.26 (3H,m), 7.21-7.15 (1H, s), 5.27 (2H, s), 4.69 (2H, s), 3.22 (2H, dd, J=8.4,16.0 Hz) 2.31 (1H, t, J=8.4 Hz), 2.28 (3H, s), 2.11 (6H, s).

According to the same manner as that of the Example 11, the followingcompound was synthesized.

TABLE 47 (VIII)

Comound No. R^(B) ¹H-NMR(d₆-DMSO) VIII-222

10.18(1H, brs), 8.77(1H, s), 8.60(1H, s), 8.19(1H, dd, J = 2.0, 11.6Hz), 7.95(1H, d, J = 3.2 Hz), 7.80(1H, d, J = 11.6 Hz), 7.67(1H, dd, J =3.2, 11.6 Hz), 7.51-7.44(1H, m), 7.35-7.26(3H, m), 7.22-7.15(1H, m),5.27(2H, s), 4.83(2H, s), 2.27(3H, s). VIII-223

10.12(1H, bs), 8.76(1H, d, J = 1.5 Hz), 8.59(1H, s), 8.20(1H, dd, J =1.8 Hz, J = 8.7 Hz), 7.96(1H, d, J = 2.4 Hz), 7.81(1H, d, J = 8.7 Hz),7.68(1H, dd, J = 2.7 Hz, J = 9.0 Hz), 7.52-7.44(1H, m), 7.35-7.16(6H,m), 5.27(2H, s), 4.65(2H, s), 2.28(3H, s). VIII-224

10.10(1H, s), 8.59(1H, s), 8.19(1H, dd, J = 2.4, 11.6 Hz), 7.95(1H, d, J= 3.2 Hz), 7.80(1H, d, J = 11.6), 7.76-7.73(1H, m), 7.68(1H, dd, J =3.6, 12 Hz), 7.48-7.44(1H, m), 7.35-7.26(3H, m), 7.21-7.15(1H, m),5.27(2H, s), 4.73(1H, t, J = 7.2 Hz), 4.70(2H, s), 3.44(2H, dd, J = 8.0,15.6 Hz), 3.21(2H, dd, J = 8.0, 15.6 Hz), 2.28(3H, s) VIII-225

10.10(1H, s), 8.76(1H, s), 8.59(1H, s), 8.19(1H, d, J = 12.0 Hz),8.08(1H, brs), 7.95(1H, s), 7.80(1H, d, J = 11.6 Hz), 7.69-7.66(1H, m),7.51-7.44(1H, m), 7.34-7.26(3H, m), 7.21-7.16(1H, s), 5.27(2H, s),4.71(2H, s), 3.60-3.53(1H, m), 2.99(3H, s), 2.28(3H, s). VIII-226

10.12(1H, s), 8.77(1H, s), 8.59(1H, s), 8.19(1H, dd, J = 2.0, 12.0 Hz),8.08(1H, brs), 7.95(1H, d, J = 3.2 Hz), 7.80(1H, d, J = 11.6 Hz),7.70-7.62(2H, m), 7.51-7.44(1H, m), 7.84-7.26(3H, m), 7.21-7.15(1H, s),5.27(2H, s), 4.69(2H, s), 3.22(2H, dd, J = 8.4, 16.0 Hz) 2.31(1H, t, J =8.4 Hz), 2.28(3H, s), 2.11(6H, s).

Example 12

(Step 1) Synthesis of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(pyrrolidin-1-yliminomethyl)quinazoline(IX-1)

In a mixture of 1 mL of tetrahydrofuran and 0.1 mL of water weredissolved 40 mg of 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)6-formylquinazoline (IV-1) and 13 mg of 1-amino-pyrrolidinehydrochloride, followed by a reaction at room temperature overnight.After the reaction, aqueous saturated sodium bicarbonate solution wasadded, followed by extraction with ethyl acetate. The organic layer wasdehydrated by passing through Presep (registered trademark), and thefiltrate was concentrated. The concentrated residue was purified bychromatography (eluting with hexane:ethyl acetate-2:1→1:1) using anamino column to obtain 38 mg of4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(pyrrolidin-1-yliminomethyl)quinazoline(IX-1) as a yellow solid.

¹H NMR (d₆-DMSO, δ): 9.76 (1H, s), 8.52 (1H, s), 8.40 (1H, brs), 8.08(1H, d, J=6.6 Hz), 8.06 (1H, d, J=1.8 Hz), 7.76 (1H, dd, J=6.6 Hz, J=1.8Hz), 7.69 (1H, dd, J=6.6 Hz), 7.50-7.45 (1H, m), 7.35-7.26 (3H, m), 7.19(1H, t, J=66 Hz), 5.26 (2H, s), 3.39 (4H, br). 1.94 (4H, br)

According to the same manner as that of Example 12, the followingcompound was synthesized.

TABLE 48 Compound No. R^(B) ¹H-NMR(d₆-DMSO) IX-2

9.86(1H, s), 8.56(1H, s), 8.55(1H, brs), 8.14(1H, d, J = 6.6 Hz),8.05(1H, d, J = 1.8 Hz), 7.78-7.74(3H, m), 7.50-7.45(1H, m),7.35-7.26(3H, m), 7.19(1H, t, J = 6.3 Hz), 5.26(2H, s), 3.18(4H, t-like,J = 3.6 Hz), 3.20(4H, t-like, J = 3.6 Hz) IX-3

9.83(1H, s), 8.56(1H, s), 8.52(1H, brs), 8.13(1H, d, J = 6.6 Hz),8.05(1H, brs), 7.77-7.73(3H,m ), 7.50-7.45(1H, m), 7.35-7.26(3H, m),7.19(1H, t, J = 6.3 Hz), 5.26(2H, s), 3.21(4H, brs), 2.53(4H, brs),2.25(3H, s) IX-4

9.83(1H, s), 8.54(1H, s), 8.50(1H, brs), 8.13(1H, d, J = 8.7 Hz),8.04(1H, d, J = 2.7 Hz), 7.76-7.70(3H, m), 7.52-7.43(1H, m),7.36-7.25(3H, m), 7.22-7.15(1H, m), 5.26(2H, s), 3.25-3.17(4H, m),1.76-1.65(4H, m), 1.58-1.49(2H, m) IX-5

9.19(3H, brs), 9.16(1H, s), 8.95(1H, brs), 8.52(1H, brs), 8.20(1H, d, J= 8.4 Hz), 7.95(1H, s), 7.79(1H, d, J = 6.9 Hz), 7.66-7.60(1H, m),7.52-7.43(1H, m), 7.36-7.14(4H, m), 5.23(2H, s) IX-6

9.73(1H, s), 8.52(1H, s), 8.38(1H, brs), 8.13(1H, d, J = 6.6 Hz),8.05(1H, d, J = 1.8 Hz), 7.75(1H, dd, J = 6.9 Hz, J = 1.8 Hz), 7.70(1H,dd, J = 6.6 Hz, J = 1.8 Hz), 7.50-7.45(1H, m), 7.33-7.26(3H, m),7.18(1H, t, J = 6.6 Hz), 5.26(2H, s), 3.72(1H, brs), 3.64(1H, dd, J =6.9 Hz, J = 2.7 Hz), 3.46(2H, dd, J = 7.2 Hz, J = 5.1 Hz), 3.13(1H, br),1.99(3H, br.), 1.80(1H, br) IX-7

10.59(1H, s), 9.84(1H, s), 8.56(1H, s), 8.53(1H, brs), 8.29(1H, d, J =6.9 Hz), 8.03(2H, brs), 7.78-7.73(2H, m), 7.51-7.45(1H, m),7.35-7.16(8H, m), 6.79(1H, t, J = 5.4 Hz), 5.27(2H, s) IX-8

9.86(1H, s), 8.61(1H, s), 8.57(1H, brs), 8.32(1H, d, J = 7.2 Hz),8.05(2H, J = 2.1 Hz), 7.80-7.73(3H, m), 7.52-7.45(3H, m), 7.37-7.28(5H,m), 7.19(1H, t, J = 6.3 Hz), 6.94(1H, t, J = 5.4 Hz), 5.27(2H, s),3.51(3H, s) IX-9

9.77(1H, s), 8.53(1H, s), 8.39(1H, brs), 8.09(1H, d, J = 6.3 Hz),8.04(1H, s), 7.75-7.69(3H, m), 7.55-7.45(2H, m), 7.34-7.26(3H, m),7.18(1H, t, J = 6.3 Hz), 5.21(2H, s), 4.69(1H, t, J = 3.6 Hz), 3.612H,dd, J = 8.4 Hz, J = 4.5 Hz), 3.29(2H, m)

TABLE 49 Compound No. R^(B) ¹H-NMR(d₆-DMSO) IX-10

(E/Z mixture) 11.51(1H, s, minor), 11.45(1H, s, major), 10.00(1H, s,major), 9.89(1H, s, minor), 8.65(1H, brs, minor), 8.60(1H, brs),8.53(1H, brs, major), 8.26(1H, d, J = 6.6 Hz, minor), 8.22(1H, d, J =6.6 Hz, major), 8.04(1H, brs, minor), 8.00(1H, d, J = 1.8 Hz, major),7.80(1H, d, J = 6.6 Hz), 7.73(1H, d, J = 6.6 Hz), 7.51-7.45(1H, m),7.35-7.27(3H, m), 7.19(1H, t, J = 6.6 Hz), 5.27(2H, s), 3.58(2H, s,minor), 3.08(2H, s, major), 2.34(3H, s, minor), 2.28(3H, s, major) IX-11

12.04(1H, s), 9.88(1H, s), 8.64(1H, brs), 8.61(1H, s), 8.31(1H, d, J =6.3 Hz), 8.17(1H, s), 8.01(1H, d, J = 2.1 Hz), 7.80(1H, d, J = 6.6 Hz),7.72(1H, d, J = 6.6 Hz), 7.50-7.45(1H, m), 7.35-7.28(3H, m), 7.19(1H, t,J = 5.4 Hz), 5.27(2H, s), 4.31(2H, s) IX-12

12.02(1H, s), 10.00(1H, s), 8.70(1H, brs), 8.65(1H, brs), 8.61(1H, s),8.31(1H, d, J = 6.0 Hz), 8.02(1H, d, J = 1.8 Hz), 7.96-7.94(2H, m),7.84(1H, d, J = 6.0 Hz), 7.72(1H, d, J = 13.8 Hz), 7.65-7.55(3H, m),7.51-7.45(1H, m), 7.35-7.28(3H, m), 7.19(1H, t, J = 6.3 Hz), 5.27(2H, s)IX-13

12.04(1H, s), 10.01(1H, s), 8.68(1H, brs), 8.65(1H, brs), 8.61(1H, s),8.28(1H, d, J = 6.9 Hz), 8.02(1H, d, J = 1.8 Hz), 7.99(1H, s), 7.83(1H,d, J = 6.6 Hz), 7.74(1H, dd, J = 6.6 Hz, J = 1.8 Hz), 7.51-7.45(1H, m),7.35-7.28(4H, m), 7.19(1H, t, J = 6.3 Hz), 6.74(1H, brs), 5.27(2H, s)IX-14

12.22(1H, s), 10.02(1H, s), 8.82(2H, m), 8.73(1H, brs), 8.65(1H, s),8.62(1H, s), 8.31(1H, d, J = 7.2 Hz), 8.01(1H, d, J = 1.8 Hz),7.86-7.84(2H, m), 7.73-7.72(2H, m), 7.51-7.45(1H, m), 7.35-7.28(3H, m),7.19(1H, t, J = 6.9 Hz), 5.27(2H, s) IX-15

12.18(1H, s), 10.01(1H, s), 9.11(1H, s), 8.80(1H, d, J = 3.3 Hz),8.72(1H, brs), 8.64-8.62(2H, m), 8.32-8.28(2H, m), 8.02(1H, d, J = 1.8Hz), 7.85(1H, d, J = 6.3 Hz), 7.73(1H, dd, J = 6.6 Hz, J = 1.8 Hz),7.62-7.59(1H, m), 7.51-7.45(1H, m), 7.35-7.28(3H, m), 7.19(1H, t, J =6.9 Hz), 5.27(2H, s)

According to the same manner as that of the above Example, the followingcompound can be synthesized. That is, in the compound represented by thefollowing general formula (A):

the following compounds represented by a combination of a group in whichR^(A) is a group selected from the following a1 to a90:

(wherein Me is methyl),a group it which R^(B) is selected from the following b1 to b6:

(wherein Me is methyl),a group in which R^(C) is selected from the following c1 to c3

a group in which R^(D) is selected from the following d1 to d22:

(wherein Me is methyl)can be synthesized.(a1, b1, c1, d1), (a1, b1, c1, d2), (a1, b1, c1, d3), (a1, b1, c1, d4),(a1, b1, c1, d5), (a1, b1, c1, d6), (a1, b1, c1, d7), (a1, b1, c1, d8),(a1, b1, c1, d9), (a1, b1, c1, d10), (a1, b1, c1, d11), (a1, b1, c1,d12), (a1, b1, c1, d13), (a1, b1, c1, d14), (a1, b1, c1, d15), (a1, b1,c1, d16), (a1, b1, c1, d17), (a1, b1, c1, d18), b1, c1, d19), (a1, b1,c1, d20), (a1, b1, c1, d21), (a1, b1, c1, d22), (a1, b1, c2, d1), (a1,b1, c2, d2), (a1, b1, c2, d3), (a1, b1, c2, d4), (a1, b1, c2, d5), (a1,b1, c2, d6), (a1, b1, c2, d7), (a1, b1, c2, d8), (a1, b1, c2, d9), (a1,b1, c2, d10), (a1, b1, c2, d11), (a1, b1, c2, d12), (a1, b1, c2, d13),(a1, b1, c2, d14), (a1, b1, c2, d15), (a1, b1, c2, d16), (a1, b1, c2,d17), (a1, b1, c2, d18), (a1, b1, c2, d19), (a1, b1, c2, d20), (a1, b1,c2, d21), (a1, b1, c2, d22), (a1, b1, c3, d1), (a1, b1, c3, d2), (a1,b1, c3, d3), (a1, b1, c3, d4), (a1, b1, c3, d5), (a1, b1, c3, d6), (a1,b1, c3, d7), (a1, b1, c3, d8), (a1, b1, c3, d9), (a1, b1, c3, d10), (a1,b1, c3, d11), (a1, b1, c3, d12), (a1, b1, c3, d13), (a1, b1, c3, d14),(a1, b1, c3, d15), (a1, b1, c3, d16), (a1, b1, c3, d17), (a1, b1, c3,d18), (a1, b1, c3, d19), (a1, b1, c3, d20), (a1, b1, c3, d21), (a1, b1,c3, d22), (a1, b2, c1, d1), (a1, b2, c1, d2), (a1, b2, c1, d3), (a1, b2,c1, d4), (a1, b2, c1, d5), (a1, b2, c1, d6), (a1, b2, c1, d7), (a1, b2,c1, d8), (a1, b2, c1, d9), (a1, b2, c1, d10), (a1, b2, c1, d11), (a1,b2, c1, d12), (a1, b2, c1, d13), (a1, b2, c1, d14), (a1, b2, c1, d15),(a1, b2, c1, d16), (a1, b2, c1, d17), (a1, b2, c1, d18), (a1, b2, c1,d19), (a1, b2, c1, d20), (a1, b2, c1, d21) (a1, b2, c1, d22), (a1, b2,c2, d1), (a1, b2, c2, d2), (a1, b2, c2, d3), (a1, b2, c2, d4), (a1, b2,c2, d5), (a1, b2, c2, d6), (a1, b2, c2, d7), (a1, b2, c2, d8), (a1, b2,c2, d9), (a1, b2, c2, d10), (a1, b2, c2, d11), (a1, b2, c2, d12), (a1,b2, c2, d13), (a1, b2, c2, d14), (a1, b2, c2, d15), (a1, b2, c2, d16),(a1, b2, c2, d17), (a1, b2, c2, d18), (a1, b2, c2, d19), (a1, b2, c2,d20), (a1, b2, c2, d21), (a1, b2, c2, d22), (a1, b2, c3, d1), (a1, b2,c3, d2), (a1, b2, c3, d3), (a1, b2, c3, d4), (a1, b2, c3, d5), (a1, b2,c3, d6), (a1, b2, c3, d7), (a1, b, b2, c3, d8), (a1, b2, c3, d9), (a1,b2, c3, d10), (a1, b2, c3, d11), (a1, b2, c3, d12), (a1, b2, c3, d13),(a1, b2, c3, d14), (a1, b2, c3, d15), (a1, b2, c3, d16), (a1, b2, c3,d17), (a1, b2, c3, d18), (a1, b2, c3, d19), (a1, b2, c3, d20), (a1, b2,c3, d21), (a1, b2, c3, d22), (a1, b3, c1, d1), (a1, b3, c1, d2), (a1,b3, c1, d3), (a1, b3, c1, d4), (a1, b3, c1, d5), (a1, b3, c1, d6), (a1,b3, c1, d7), (a1, b3, c1, d8), (a1, b3, c1, d9), (a., b3, c1, d10), (a1,b3, c1, d11), (a1, b3, c1, d12), (a1, b3, c1, d13), (a1, b3, c1, d14),(a1, b3, c1, d15), (a1, b3, c1, d16), (a1, b3, c1, d17), (a1, b3, c1,d18), (a1, b3, c1, d19), (a1, b3, c1, d20), (a1, b3, c1, d21), (a1, b3,c1, d22), (a1, b3, c2, d1), (a1, b3, c2, d2), (a1, b3, c2, d3), (a1, b3,c2, d4), (a1, b3, c2, d5), (a1, b3, c2, d6), (a1, b3, c2, d7), (a1, b3,c2, d3), (a1, b3, c2, d9), (a1, b3, c2, d10), (a1, b3, c2, d11), (a1,b3, c2, d12), (a1, b3, c2, d13), (a1, b3, c2, d14), (a1, b3, c2, d15),(a1, b3, c2, d16), (a1, b3, c2, d17), (a1, b3, c2, d18), (a1, b3, c2,d19), (a1, b3, c2, d20), (a1, b3, c2, d21), (a1, b3, c2, d22), (a1, b3,c3, d1), (a1, b3, c3, d2), (a1, b3, c3, d3), (a1, b3, c3, d4), (a1, b3,c3, d5), (a1, b3, c3, d6), (a1, b3, c3, d7), (a1, b3, c3, d3), (a1, b3,c3, d9), (a1, b3, c3, d10), (a1, b3, c3, d11), (a1, b3, c3, d12), (a1,b3, c3, d13), (a1, b3, c3, d14), (a1, b3, c3, d15), (a1, b3, c3, d16),(a1, b3, c3, d17), (a1, b3, c3, d18), (a1, b3, c3, d19), (a1, b3, c3,d20), (a1, b3, c3, d21), (a1, b3, c3, d22), (a1, b4, c1, d1), (a1, b4,c1, d2), (a1, b4, c1, d3), (a1, b4, c1, d4), (a1, b4, c1, d5), (a1, b4,c1, d6), (a1, b4, c1, d7), (a1, b4, c1, d8), (a1, b4, c1, d9), (a1, b4,c1, d10), (a1, b4, c1, d11), (a1, b4, c1, d12), (a1, b4, c1, d13), (a1,b4, c1, d14), (a1, b4, c1, d15), (a1, b4, c1, d16), (a1, b4, c1, d17),(a1, b4, c1, d13), (a1, b4, c1, d19), (a1, b4, c1, d20), (a1, b4, c1,d21), (a1, b4, c1, d22), (a1, b4, c2, d1), (c1, b4, c2, d2), (a1, b4,c2, c3), (a1, b4, c2, d4), (a1, b4, c2, d5), (a1, b4, c2, d6), (c1, b4,c2, d7), (a1, b4, c2, d8), (a1, b4, c2, d9), (a1, b4, c2, d10), (a1, b4,c2, d11), (a1, b4, c2, d12), (a1, b4, c2, d13), (a1, b4, c2, d14), (a1,b4, c2, d15), (a1, b4, c2, d16), (a1, b4, c2, d17), (a1, b4, c2, d18),(a1, b4, c2, d19), (a1, b4, c2, d20), (a1, b4, c2, d21), (a1, b4, c2,d22), (a1, b4, c3, d1), (a1, b4, c3, d2), (a1, b4, c3, d3), (a1, b4, c3,d4), (a1, b4, c3, d5), (a1, b4, c3, d6), (a1, b4, c3, d7), (a1, b4, c3,d8), (a1, b4, c3, d9), (a1, b4, c3, d10), (a1, b4, c3, d11), (a1, b4,c3, d12), (a1, b4, c3, d13), (a1, b4, c3, d14), (a1, b4, c3, d15), (a1,b4, c3, d16), (a1, b4, c3, d17), (a1, b4, c3, d18), (a1, b4, c3, d19),(a1, b4, c3, d20), (c1, b4, c3, d21), (a1, b4, c3, d22), (a1, b5, c1,d1), (a1, b5, c1, d2), (a1, b5, c1, d3), (a1, b5, c1, d4), (a1, b5, c1,d5), (a1, b5, c1, d6), (a1, b5, c1, d7), (a1, b5, c1, d8), (a1, b5, c1,d9), (a1, b5, c1, d10), (a1, b5, c1, d11), (a1, b5, c1, d12), (a1, b5,c1, d13), (a1, b5, c1, d14), (a1, b5, c1, d15), (a1, b5, c1, d16), (a1,b5, c1, d17), (a1, b5, c1, d18), (a1, b5, c1, d19), (a1, b5, c1, d20),(a1, b5, c1, d21), (a1, b5, c1, d22), (a1, b5, c2, d1), (a1, b5, c2,d2), (a1, b5, c2, d3), (a1, b5, c2, d4), (a1, b5, c2, d5), (a1, b5, c2,d6), (a1, b5, c2, d7), (a1, b5, c2, d8), (a1, b5, c2, d9), (a1, b5, c2,d10), (a1, b5, c2, d11), (a1, b5, c2, d12), (a1, b5, c2, d13), (a1, b5,c2, d14), (a1, b5, c2, d15), (a1, b5, c2, d16), (a1, b5, c2, d17), (a1,b5, c2, d18), (a1, b5, c2, d19), (a1, b5, c2, d20), (a1, b5, c2, d21),(a1, b5, c2, d22), (a1, b5, c3, d1), (a1, b5, c3, d2), (a1, b5, c3, d3),(a1, b5, c3, d4), (a1, b5, c3, d5), (a1, b5, c3, d6), (a1, b5, c3, d7),(a1, b5, c3, d8), (a1, b5, c3, d9), (a1, b5, c3 d10), (a1, b5, c3, d11),(a1, b5, c3, d12), (a1, b5, c3, d13), (a1, b5, c3, d14), a1, b5, c3,d15), a1, b5, c3, d16), a1, b5, c3, d17), a1, b5, c3, d18), a1, b5, c3,d19), a1, b5, b3, d20), a1, b5, c3, d21), a1, b5, c3, d22), (a1, b6, c1,d1), (a1, b6, c1, d2), (a1, b6, c1, d3), (a1, b6, c1, d4), (a1, b6, c1,d5), (a1, b6, c1, d6), (a1, b6, c1, d7), (a1, b6, c1, d8), (a1, b6, c1,d9), (a1, b6, c1, d10), (a1, b6, c1, d11), (a1, b6, c1, d12), (a1, b6,c1, d13), (a1, b6, c1, d14), (a1, b6, c1, d15), (a1, b6, c1, d16), (a1,b6, c1, d17), (a1, b6, c1, d18), (a1, b6, c1, d19), (a1, b6, c1, d20),(a1, b6, c1, d21), (a1, b6, c1, d22), (a1, b6, c2, d1), (a1, b6, c2,d2), (a1, b6, c2, d3), (a1, b6, c2, d4), (a1, b6, c2, d5), (a1, b6, c2,d6), (, b6, c2, d7), (a1, b6, c2, d8), (a1, b6, c2, d9), (a1, b6, c2,d10), (a1, b6, c2, d11), (a1, b6, c2, d12), (a1, b6, c2, d13), (a1, b6,c2, d14), (a1, b6, c2, d15), (a1, b6, c2, d16), (a1, b6, c2, d17), (a1,b6, c2, d18), (a1, b6, c2, d19), (a1, b6, c2, d20), (a1, b6, c2, d22),(a1, b6, c3, d1), (a1, b6, c3, d1), (a1, b6, c3, d1), (a1, b6, c3, d1),(a1, b6, c3, d1), (a1, b6, c3, d11), (a1, b6, c3, d1), (a1, b6, c3, d1),(a1, b6, c3, d1), (a1, b6, c3, d1), (a1, b6, c3, (a1, b6, c3, d12), (a1,b6, c3, d13), (a1, b6, c3, d14), (a1, b6, c3, d15), (a1, b6, c3, d16),(a1, b6, c3, d17), (a1, b6, c3, d18), (a1, b6, c3, d19), (a1, b6, c3,d20), (c1, b6, c3, d21), (a1, b6, c3, d22), (c2, b1, c1, d1), (a2, b1,c1, d2), (a2, b1, c1, d3), (a2, b1, c1, d4), (a2, b1, c1, d5), (a2, b1,c1, d6), (a2, b1, c1, d7), (a2, b1, c1, d8), (a2, b1, c1, d9), (a2, b1,c1, d10), (a2, b1, c1, d11), (a2, b1, c1, d12), (a2, b1, c1, d13), (a2,b1, c1, d14), (a2, b1, c1, d15), (a2, b1, c1, d16), (a2, b1, c1, d17),(a2, b1, c1, d18), (a2, b1, c1, d19), (a2, b1, c1, d20), (a2, b1, c1,d21), (a2, b1, c1, d22), (a2, b1, c2, d1), (a2, b1, c2, d2), (a2, b1,c2, d3), (a2, b1, c2, d4), (a2, b1, c2, d5), (a2, b1, c2, d6), (a2, b1,c2, d7), (a2, b1, c2, d8), (a2, b1, c2, d9), (a2, b1, c2, d10), (a2, b1,c2, d11), (a2, b1, c2, d12), (a2, b1, c2, d13), (a2, b1, c2, d14), (a2,b1, c2, d15), (a2, b1, c2, d16), (a2, b1, c2, d17), (a2, b1, c2, d18),(a2, b1, c2, d19), (a2, b1, c2, d20), (a2, b1, c2, d21), (a2, b1, c2,d22), (a2, b1, c3, d1), (a2, b1, c3, d2), (a2, b1, c3, d3), (a2, b1, c3,d4), (a2, b1, c3, d5), (a2, b1, c3, d6), (a2, b1, c3, d7), (a2, b1, c3,d8), (a2, b1, c3, d9), (a2, b1, c3, d10), (a2, b1, c3, d11), (a2, b1,c3, d12), (a2, b1, c3, d13), (a2, b1, c3, d14), (a2, b1, c3, d15), (a2,b1, c3, d16), (a2, b1, c3, d17), (a2, b1, c3, d18), (a2, b1, c3, d19),(a2, b1, c3, d20), (a2, b1, c3, d21), (a2, b1, c3, d22), (a2, b2, c1,d1), (a2, b2, c1, d2), (a2, b2, c1, d3), (a2, b2, c1, d4), (a2, b2, c1,d5), (a2, b2, c1, d6), (a2, b2, c1, d7), (a2, b2, c1, d8), (a2, b2, c1,d9), (a2, b2, c1, d10), (a2, b2, c1, d11), (a2, b2, c1, d12), (a2, b2,c1, d13), (a2, b2, c1, d14), (a2, b2, c1, d15), (a2, b2, c1, d16), (a2,b2, c1, d17), (a2, b2, c1, d18), (a2, b2, c1, d19), (a2, b2, c1, d20),(a2, b2, c1, d21), (a2, b2, c1, d22), (a2, b2, c2, d1), (a2, b2, c2,d2), (a2, b2, c2, d3), (a2, b2, c2, d4), (a2, b2, c2, d5), (a2, b2, c2,d6), (a2, b2, c2, d7), (a2, b2, c2, d8), (a2, b2, c2, d9), (a2, b2, c2,d10), (a2, b2, c2, d11), (a2, b2, c2, d12), (a2, b2, c2, d13), (a2, b2,c2, d24), (a2, b2, c2, d15), (a2, b2, c2, d16), (a2, b2, c2, d17), (a2,b2, c2, d18), (a2, b2, c2, d19), (a2, b2, c2, d20), (a2, b2, c2, d21)(a2, b2, c2, d22), (a2, b2, c3, d1), (a2, b2, c3, d2), (a2, b2, c3, d3),(a2, b2, c3, d4), (a2, b2, c3, d5), (a2, b2, c3, d6), (a2, b2, c3, d7),(a2, b2, c3, d8), (a2, b2, c3, d9), (a2, b2, c3, d10), (a2, b2, c3,d11), (a2, b2, c3, d12), (a2, b2, c3, d13), (a2, b2, c3, d14), (a2, b2,c3, d15), (a2, b2, c3, d16), (a2, b2, c3, d17), (a2, b2, c3, d18), (a2,b2, c3, d19), (a2, b2, c3, d20), (a2, b2, c3, d21), (a2, b2, c3, d22),(a2, b3, c1, d1), (a2, b3, c1, d2), (a2, b3, c1, d3), (a2, b3, c1, d4),(a2, b3, c1, d5), (a2, b3, c1, d6), (a2, b3, c1, d7), (a2, b3, c1, d8),(a2, b3, c1, d9), (a2, b3, c1, d10), (a2, b3, c1, d11), (a2, b3, c1,d12), (a2, b3, c1, d13), (a2, b3, c1, d14), (a2, b3, c1, d15), (a2, b3,c1, d16), (a2, b3, c1, d17), (a2, b3, c1, d18), (a2, b3, c1, d19), (a2,b3, c1, d20), (a2, b3, c1, d21), (a2, b3, c1, d22), (a2, b3, c2, d1),(a2, b3, c2, d2), (a2, b3, c2, d3), (a2, b3, c2, d4), (a2, b3, c2, d5),(a2, b3, c2, d6), (a2, b3, c2, d7), (a2, b3, c2, d8), (a2, b3, c2, d9),(a2, b3, c2, d10), (a2, b3, c2, d11), (a2, b3, c2, d12), (a2, b3, c2,d13), (a2, b3, c2, d14), (a2, b3, c2, d15), (a2, b3, c2, d16), (a2, b3,c2, d17), (a2, b3, c2, d18), (a2, b3, c2, d19), (a2, b3, c2, d20), (a2,b3, c2, d21), (a2, b3, c2, d22), (a2, b3, c3, d1), (a2, b3, c3, d2),(a2, b3, c3, d3), (a2, b3, c3, d4), (a2, b3, c3, d5), (a2, b3, c3, d6),(a2, b3, c3, d7), (a2, b3, c3, d8), (a2, b3, c3, d9), (a2, b3, c3, d10),(a2, b3, c3, d11), (a2, b3, c3, d12), (a2, b3, c3, d13), (a2, b3, c3,d14), (a2, b3, c3, d15), (a2, b3, c3, d16), (a2, b3, c3, d17), (a2, b3,c3, d18), (a2, b3, c3, d19), (a2, b3, c3, d20), (a2, b3, c3, d21), (a2,b3, c3, d22), (a2, b4, c1, d1), (a2, b4, c1, d2), (a2, b4, c1, d3), (a2,b4, c1, d4), (a2, b4, c1, d5), (a2, b4, c1, d6), (a2, b4, c1, d7), (a2,b4, c1, d8), (a2, b4, c1, d9), (a2, b4, c1, d10), (a2, b4, c1, d11),(a2, b4, c1, d12), (a2, b4, c1, d13), (a2, b4, c1, d14), (a2, b4, c1,d15), (a2, b4, c1, d16), (a2, b4, c1, d17), (a2, b4, c1, d18), (a2, b4,c1, d19), (a2, b4, c1, d20), (a2, b4, c1, d21), (a2, b4, c1, d22), (a2,b4, c2, d1), (a2, b4, c2, d2), (a2, b4, c2, d3), (a2, b4, c2, d4), (a2,b4, c2, d15), (a2, b4, c2, d6), (a2, b4, c2, d7), (a2, b4, c2, d8), (a2,b4, c2, d9), (a2, b4, c2, d10), (a2, b4, c2, d11), (a2, b4, c2, d12),(a2, b4, c2, d13), (a2, b4, c2, d14), (a2, b4, c2, d15), (a2, b4, c2,d16), (a2, b4, c2, d17), (a2, b4, c2, d18), (a2, b4, c2, d19), (a2, b4,c2, d20), (a2, b4, c2, d21), (a2, b4, c2, d22), (a2, b4, c3, d1), (a2,b4, c3, d2), (a2, b4, c3, d3), (a2, b4, c3, d4), (a2, b4, c3, d5), (a2,b4, c3, d6), (a2, b4, c3, d7), (a2, b4, c3, d8), (a2, b4, c3, d9), (a2,b4, c3, d10), (a2, b4, c3, d11), (a2, b4, c3, d12), (a2, b4, c3, d13),(a2, b4, c3, d14), (a2, b4, c3, d15), (a2, b4, c3, d16), (a2, b4, c3,d17), (a2, b4, c3, d18), (a2, b4, c3, d19), (a2, b4, c3, d20), (a2, b4,c3, d21), (a2, b4, c3, d22), (a2, b5, c1, d1), (a2, b5, c1, d2), (a2,b5, c1, d3), (a2, b5, c1, d4), (a2, b5, c1, d5), (a2, b5, c1, d6), (a2,b5, c1, d7), (a2, b5, c1, d8), (a2, b5, c1, d9), (a2, b5, c1, d10), (a2,b5, c1, d11), (a2, b5, c1, d12), (a2, b5, c1, d13), (a2, b5, c1, d14),(a2, b5, c1, d15), (a2, b5, c1, d16), (a2, b5, c5, d17), (a2, b5, c5,d18), (a2, b5, c1, d19), (a2, b5, c1, d20), (a2, b5, c1, d21), (a2, b5,c1, d22), (a2, b5, c2, d1), (a2, b5, c2, d2), (a2, b5, c2, d3), (a2, b5,c2, d4), (a2, b5, c2, d5), (a2, b5, c2, d6), (a2, b5, c2, d7), (a2, b5,c2, d8), (a2, b5, c2, d9), (a2, b5, c2, d10), (a2, b5, c2, d11), (a2,b5, c2, d12), (a2, b5, c2, d13), (a2, b5, c2, d14), (a2, b5, c2, d15),(a2, b5, c2, d16), (a2, b5, c2, d17), (a2, b5, c2, d18), (a2, b5, c2,d19), (a2, b5, c2, d20), (a2, b5, c2, d21), (a2, b5, c2, d22), (a2, b5,c3, d1), (a2, b5, c3, d2), (a2, b5, c3, d3), (a2, b5, c3, d4), (a2, b5,c3, d5), (a2, b5, c3, d6), (a2, b5, c3, d7), (a2, b, c3, d8), (a2, b5,c3, d9), (a2, b5, c3, d10), (a2, b5, c3, d11), (a2, b5, c3, d12), (a2,b5, c3, d13), (a2, b5, c3, d14), (a2, b5, c3, d15), (a2, b5, c3, d16),(a2, b5, c3, d17), (a2, b5, c3, d18), (a2, b3, c3, d19), (a2, b3, c3,d20), (a2, b3, c3, d21), (a2, b3, c3, d22), (a2, b6, c1, d1), (a2, b6,c1, d2), (a2, b6, c1, d3), (a2, b6, c1, d4), (a2, b6, c1, d5), (a2, b6,c1, d6), (a2, c1, d7), (a2, b6, c1, d8), (a2, b6, c1, d9), (a2, b6, c1,d10), (a2, b6, c1, d11), (a2, b6, c1, d12), (a2, b6, c1, d13), (a2, b6,c1, d14), (a2, b6, c1, d15), (a2, b6, c1, d16), (a2, b6, c1, d17), (a2,b6, c1, d18), (a2, b6, c1, d19), (a2, b6, c1, d20), (a2, b6, c1, d21),(a2, b6, c1, d22), (a2, b6, c2, d1), (a2, b6, c2, d2), (a2, b6, c2, d3),(a2, b6, c2, d4), (a2, b6, c2, d5), (a2, b6, c2, d6), (a2, b6, c2, d7),(a2, b6, c2, d8), (a2, b6, c2, d9), (a2, b6, c2, d10), (a2, b6, c2,d11), (a2, b6, c2, d12), (a2, b6, c2, d13), (a2, b6, c2, d14), (a2, b6,c2, d15), 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c2, d4), (a3, b1, c2, d5), (a3, b1, c2, d6),(a3, b1, c2, d7), (a3, b1, c2, d8), (a3, b1, c2, d9), (a3, b1, c2, d10),(a3, b1, c2, d11), (a3, b1, c2, d12), (a3, b1, c2, d13), (a3, b1, c2,d14), (a3, b1, c2, d15), (a3, b1, c2, d16), (a3, b1, c2, d17), (a3, b1,c2, d18), (a3, b1, c2, d19), (a3, b1, c2, d20), (a3, b1, c2, d21), (a3,b1, c2, d22), (a3, b1, c3, d1), (a3, b1, c3, d2), (a3, b1, c3, d3), (a3,b1, c3, d4), (a3, b1, c3, d5), (a3, b1, c3, d6), (a3, b1, c3, d7), (a3,b1, c3, d8), (a3, b1, c3, d9), (a3, b1, c3, d10), (a3, b1, c3, d11),(a3, b1, c3, d12), (a3, b1, c3, d13), (a3, b1, c3, d14), (a3, b1, c3,d15), (a3, b1, c3, d16), (a3, b1, c3, d17), (a3, b1, c3, d18), (a3, b1,c3, d19), (a3, b1, c3, d20), (a3, b1, c3, d21), (a3, b1, c3, d22), (a3,b2, c1, d1), (a3, b2, c1, d2), (a3, b2, c1, d3), (a3, b2, c1, d4), (a3,b2, c1, d5), (a3, b2, c1, d6), (a3, b2, c1, d7), (a3, b2, c1, d8), (a3,b2, c1, c9), (a3, b2, c1, d10), (a3, b2, c1, d11), (a3, b2, c1, d12),(a3, b2, c1, d13), (a3, b2, c1, d14), 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c1, d3), (a3, b3,c1, d4), (a3, b3, c1, d5), (a3, b3, c1, d6), (a3, b3, c1, d7), (a3, b3,c1, d8), (a3, b3, c1, d9), (a3, b3, c1, d10), (a3, b3, c1, d11), (a3,b3, c1, d12), (a3, b3, c1, d13), (a3, b3, c1, d14), (a3, b3, c1, d15),(a3, b3, c1, d16), (a3, b3, c1, d17), (a3, b3, c1, d18), (a3, b3, c1,d19), (a3, b3, c1, d20), (a3, b3, c1, d21), (a3, b3, c1, d22), (a3, b3,c2, d1), (a3, b3, c2, d2), (a3, b3, c2, d3), (a3, b3, c2, d4), (a3, b3,c2, d5), (a3, b3, c2, d6), (a3, b3, c2, d7), (a3, b3, c2, d8), (a3, b3,c2, d9), (a3, b3, c2, d10), (a3, b3, c2, d11), (a3, b3, c2, d12), (a3,b3, c2, d13), (a3, b3, c2, d14), (a3, b3, c2, d15), (a3, b3, c2, d16),(a3, b3, c2, d17), (a3, b3, c2, d18), (a3, b3, c2, d19), (as, b, c2,d20), (a3, b3, c2, d21), (a3, b3, c2, d22), (a3, b3, c3, d1), (a3, b3,c3, d2), (a3, b3, c3, d3), (a3, b3, c3, d4), (a3, b3, c3, d5), (a3, b3,c3, d6), (a3, b3, c3, d7), (a3, b3, c3, d8), (a3, b3, c3, d9), (a3, b3,c3, d10), (a3, b3, c3, d11), (a3, b3, c3, d12), (a3, b3, c3, d13), 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b1, c2, d6), (a7, b1, c2, d7), (a7, b1, c2, d8), (a7, b1, c2, d9),(a7, b1, c2, d10), (a7, b1, c2, d11), (a7, b1, c2, d12), (a7, b1, c2,d13), (a7, b1, c2, d14), (a7, b1, c2, d15), (a7, b1, c2, d16), (a7, b1,c2, d17), (a7, b1, c2, d18), (a7, b1, c2, d19), (a7, b1, c2, d20), (a7,b1, c2, d21), (a7, b1, c2, d22), (a7, b1, c3, d1), (a7, b1, c3, d2),(a7, b1, c3, d3), (a7, b1, c3, d4), (a7, b1, c3, d5), (a7, b1, c3, d6),(a7, b1, c3, d7), (a7, b1, c3, d8), (a7, b1, c3, d9), (a7, b, c3, d10),(a7, b1, c3, d8), (a7, b1, c3, d12), (a7, b1, c3, d13), (a7, b1, c3,d14), (a7, b1, c3, d15), (a7, b1, c3, d16), (a7, b1, c3, d17), (a7, b1,c3, d18), (a7, b1, c3, d19), (a7, b1, c3, d20), (a7, b1, c3, d21), (a7,b1, c3, d22), (a7, b2, c1, d1), (a7, b2, c1, d2), (a7, b2, c1, d3), (a7,b2, c1, d4), (a7, b2, c1, d5), (a7, b2, c1, d6), (a1, b2, c1, d7), (a7,b2, c1, d8), (a7, b2, c1, d9), (a7, b2, c1, d10), (a7, b2, c1, d11),(a7, b2, c1, d12), (a7, b2, c1, d13), (a7, b2, c1, d14), (a7, b2, c1,d15), (a7, b2, c1, d16), (a7, b2, c1, d17), (a7, b2, c1, d18), (a7, b2,c1, d19), (a7, b2, c1, d20), (a7, b2, c1, d21), (a7, b2, c1, d22), (a7,b2, c2, d1), (a7, b2, c2, d2), (a7, b2, c2, d3), (a7, b2, c2, d4), (a7,b2, c2, d5), (a7, b2, c2, d6), (a7, b2, c2, d7), (a7, b2, c2, d8), (a7,b2, c2, d9), (a7, b2, c2, d10), (a7, b2, c2, d11), (a7, b2, c2, d12),(a7, b2, c2, d13), (a7, b2, c2, d14), (a7, b2, c2, d15), (a7, b2, c2,d16), (a7, b2, c2, d17), (a7, b2, c2, d18), (a7, b2, c2, d19), (a7, b2,c2, d20), (a7, b2, c2, d21), (a7, b2, c2, d22), (a7, b2, c3, d1), (a7,b2, c3, d2), (a7, b2, c3, d3), (a7, b2, c3, d4), (a7, b2, c3, d5), (a7,b2, c3, d6), (a7, b2, c3, d7), (a7, b2, c3, d8), (a7, b2, c3, d9), (a7,b2, c3, d10), (a7, b2, c3, d11), (a7, b2, c3, d12), (a7, b2, c3, d13),(a7, b2, c3, d14), (a7, b2, c3, d15), (a7, b2, c3, d16), (a7, b2, c3,d17), (a7, b2, c3, d18), (a7, b2, c3, d19), (a7, b2, c3, d20), (a7, b2,c3, d21), (a7, b2, c3, d22), (a7, b3, c1, d1), (a7, b3, c1, d2), (a7,b3, c1, d3), (a7, b3, c1, d4), (a7, b3, c1, d5), (a7, b3, c1, d6), (a7,b3, c1, d7), (a7, b3, c1, d8), (a7, b3, c1, d9), (a7, b3, c1, d10), (a7,b3, c1, d11), (a7, b3, c1, d12), (a7, b3, c1, d13), (a7, b3, c1, d14),(a7, b3, c1, d15), (a7, b3, c1, d16), (a7, b3, c1, d17), (a7, b3, c1,d18), (a7, b3, c1, d19), (a7, b3, c1, d20), (a7, b3, c1, d21), (a7, b3,c1, d22), (a7, b3, c2, d1), (a7, b3, c2, d2), (a7, b3, c2, d3), (a7, b3,c2, d4), (a7, b3, c2, d5), (a7, b3, c2, d6), (a7, b3, c2, d7), (a7, b3,c2, d8), (a7, b3, c2, d9), (a7, b3, c2, d10), (a7, b3, c2, d11), (a7,b3, c2, d12), (a7, b3, c2, d13), (a7, b3, c2, d14), (a7, b3, c2, d15),(a7, b3, c2, d16), (a7, b3, c2, d17), (a7, b3, c2, d18), (a7, b3, c2,d19), (a7, b3, c2, d20), (a7, b3, c2, d21), (a7, b3, c2, d22), (a7, b3,c3, d1), (a7, b3, c3, d2), (a7, b3, c3, d3), (a7, b3, c3, d4), (a7, b3,c3, d5), (a7, b3, c3, d6), (a7, b3, c3, d7), (a7, b3, c3, d8), (a7, b3,c3, d9), (a7, b3, c3, d10), (a7, b3, c3, d11), (a7, b3, c3, d12), (a7,b3, c3, d13), (a7, b3, c3, d14), (a7, b3, c3, d15), (a7, b3, c3, d16),(a7, b3, c3, d17), (a7, b3, c3, d18), (a7, b3, c3, d19), (a7, b3, c3,d20), (a7, b3, c3, d21), (a7, b3, c3, d22), (a7, b4, c1, d1), (a7, b4,c1, d2), (a7, b4, c1, d3), (a7, b4, c1, d4), (a7, b4, c1, d5), (a7, b4,c1, d6), (a7, b4, c1, d7), (a7, b4, c1, d8), (a7, b4, c1, d9), (a7, b4,c1, d10), (a7, b4, c1, d11), (a7, b4, c1, d12), (a7, b4, c1, d13), (a7,b4, c1, d14), (a7, b4, c1, d15), (a7, b4, c1, d16), (a7, b4, c1, d17),(a7, b4, c1, d18), (a7, b4, c1, d19), (a7, b4, c1, d20), (a7, b4, c1,d21), (a7, b4, c1, d22), (a7, b4, c2, d1), (a7, b4, c2, d2), (a7, b4,c2, d3), (a7, b4, c2, d4), (a7, b4, c2, d5), (a7, b4, c2, d6), (a7, b4,c2, d7), (a7, b4, c2, d8), (a7, b4, c2, d9), (a7, b4, c2, d10), (a7, b4,c2, d11), (a7, b4, c2, d12), (a7, b4, c2, d13), (a7, b4, c2, d14), (a7,b4, c2, d15), (a7, b4, c2, d16), (a7, b4, c2, d17), (a7, b4, c2, d18),(a7, b4, c2, d19), (a7, b4, c2, d20), (a7, b4, c2, d21), (a7, b4, c2,d22), (a7, b4, c3, d1), (a7, b4, c3, d2), (a7, b4, c3, d3), (a7, b4, c3,d4), (a7, b4, c3, d5), (a7, b4, c3, d6), (a7, b4, c3, d7), (a7, b4, c3,d8), (a7, b4, c3, d9), (a7, b4, c3, d10), (a7, b4, c3, d11), (a7, b4,c3, d12), (a7, b4, c3, d13), (a7, b4, c3, d14), (a7, b4, c3, d15), (a7,b4, c3, d16), (a7, b4, c3, d17), (a7, b4, c3, d18), (a7, b4, c3, d19),(a7, b4, c3, d20), (a7, b4, c3, d21), (a7, b4, c3, d22), (a7, b5, c1,d1), (a7, b5, c1, d2), (a7, b5, c1, d3), (a7, b5, c1, d4), (a7, b5, c1,d5), (a7, b5, c1, d6), (a7, b5, c1, d7), (a7, b5, c1, d8), (a7, b5, c1,d9), (a7, b5, c1, d10), (a7, b5, c1, d11), (a7, b5, c1, d12), (a7, b5,c1, d13), (a7, b5, c1, d14), (a7, b5, c1, d15), (a7, b5, c1, d16), (a7,b5, c1, d17), (a7, b5, c1, d18), (a7, b5, c1, d19), (a7, b5, c1, d20),(a7, b5, c1, d21), (a7, b5, c1, d22), (a7, b5, c2, d1), (a7, b5, c2,d2), (a7, b5, c2, d3), (a7, b5, c2, d4), (a7, b5, c2, d5), (a7, b5, c2,d6), (a7, b5, c2, d7), (a7, b5, c2, d8), (a7, b5, c2, d9), (a7, b5, c2,d10), (a7, b5, c2, d11), (a7, b5, c2, d12), (a7, b5, c2, d13), (a7, b5,c2, d14), (a7, b5, c2, d15), (a7, b5, c2, d16), (a7, b5, c2, d17), (a7,b5, c2, d18), (a7, b5, c2, d19), (a7, b5, c2, d20), (a7, b5, c2, d21),(a7, b5, c2, d22), (a7, b5, c3, d1), (a7, b5, c3, d2), (a7, b5, c3, d3),(a7, b5, c3, d4), (a7, b5, c3, d5), (a7, b5, c3, d6), (a7, b5, c3, d7),(a7, b5, c3, d8), (a7, b6, c3, d9), (a7, b5, c3, d10), (a7, b5, c3,d11), (a7, b5, c3, d12), (a7, b5, c3, d13), (a7, b5, c3, d14), (a7, b5,c3, d15), (a7, b5, c3, d16), (a7, b5, c3, d17), (a7, b5, c3, d18), (a7,b5, c3, d19), (a7, b5, c3, d20), (a7, b5, c3, d21), (a7, b5, c3, d22),(a7, b6, c1, d1), (a7, b6, c1, d2), (a7, b6, c1, d3), (a7, b6, c1, d4),(a7, b6, c1, d5), (a7, b6, c1, d6), (a7, b6, c1, d7), (a7, b6, c1, d8),(a7, b6, c1, d9), (a7, b6, c1, d10), (a7, b6, c1, d11), (a7, b6, c1,d12), (a7, b6, c1, d13), (a7, b6, c1, d14), (a7, b6, c1, d15), (a7, b6,c1, d16), (a7, b6, c1, d17), (a7, b6, c1, d18), (a7, b6, c1, d19), (a7,b6, c1, d20), (a7, b6, c1, d21), (a7, b6, c1, d22), (a7, b6, c2, d1),(a7, b6, c2, d2), (a7, b6, c2, d3), (a7, b6, c2, d4), (a7, b6, c2, d5),(a7, b6, c2, d6), (a7, b6, c2, d7), (a7, b6, c2, d8), (a7, b6, c2, d9),(a7, b6, c2, d10), (a7, b6, c2, d11), (a7, b6, c2, d12), (a7, b6, c2,d13), (a7, b6, c2, d14), (a7, b6, c2, d15), (a7, b6, c2, d16), (a7, b6,c2, d17), (a7, b6, c2, d18), (a7, b6, c2, d19), (a7, b6, c2, d20), (a,b6, c2, d21), (a7, b6, c2, d22), (a7, b6, c3, d1), (a7, b6, c3, d2),(a7, b6, c3, d3), (a7, b6, c3, d4), (a7, b6, c3, d5), (a7, b6, c3, d6),(a7, b6, c3, d7), (a7, b6, c3, d8), (a7, b6, c3, d9), (a7, b6, c3, d10),(a7, b6, c3, d11), (a7, b6, c3, d12), (a7, b6, c3, d13), (a7, b6, c3,d14), (a7, b6, c3, d15), (a7, b6, c3, d16), (a7, b6, c3, d7), (a7, b6,c3, d18), (a7, b6, c3, d19), (a7, b6, c3, d20), (a7, b6, c3, d21), (a7,b6, c3, d22), (a8, b1, c1, d1), (a8, b1, c1, d2), (a8, b1, d3), (a8, b1,c1, d4), (a3, b1, c1, d5), (a8, b1, c1, d6), (a8, b1, c1, d7), (a8, b1,c1, d8), (a8, b1, c1, d9), (a8, b1, c1, d10), (a8, b1, c1, d11), (a8,b1, c1, d12), (a8, b1, c1, d13), (a8, b1, c1, d14), (a8, b1, c1, d16),(a8, b1, c1, d16), (a8, b1, c1, d17), (a8, b1, c1, d18), (a8, b1, c1,d19), (a8, b1, c1, d20), (a8, b1, c1, d21), (a8, b1, c1, d22), (a8, b1,c2, d1), (a8, b1, c2, d2), (a8, b1, c2, d3), (a8, b1, c2, d4), (a8, b1,c2, d5), (a8, b1, c2, d6), (a8, b1, c2, d7), (a8, b1, c2, d8), (a8, b1,c2, d9), (a8, b1, c2, d10), (a8, b1, c2, d11), (a8, b1, c2, d12), (a8,b1, c2, d13), (a8, b1, c2, d14), (a8, b1, c2, d15), (a8, b1, c2, d16),(a8, b1, c2, d17), (a8, b1, c2, d18), (a8, b1, c2, d19), (a8, b1, c2,d20), (a8, b1, c2, d21), (a8, b1, c2, d22), (a8, b1, c3, d1), (a8, b1,c3, d2), (a8, b1, c3, d3), (a8, b1, c3, d4), (a8, b1, c3, d5), (a8, b1,c3, d6), (a8, b1, c3, d7), (a8, b1, c3, d8), (a8, b1, c3, d9), (a8, b1,b3, d10), (a8, b1, c3, d11), (a8, b1, c3, d12), (a8, b1, c3, d13), (a8,b1, c3, d14), (a8, b1, c3, d15), (a8, b1, c3, d16), (a8, b1, c3, d17),(a8, b1, c3, d18), (a8, b1, c3, d19), (a8, b1, c3, d20), (a8, b1, c3,d21), (a8, b1, c3, d22), (a8, b2, c1, d1), (a8, b2, c1, d2), (a8, b2,c1, d3), (a8, b2, c1, d4), (a8, b2, c1, d5), (a8, b2, c1, d6), (a8, b2,c1, d7), (a8, b2, c1, d8), (a8, b2, c1, d9), (a8, b2, c1, d10), (a8, b2,c1, d11), (a8, b2, c1, d12), (a8, b2, c1, d13), (a8, b2, c1, d14), (a8,b2, c1, d15), (a8, b2, c1, d16), (a8, b2, c1, d17), (a8, b2, c1, d18),(a8, b2, c1, d19), (a8, b2, c1, d20), (a8, b2, c1, d21), (a8, b2, c1,d22), (a8, b2, c2, d1), (a8, b2, c2, d2), (a8, b2, c2, d3), (a8, b2, c2,d4), (a8, b2, c2, d5), (a8, b2, c2, d6), (a8, b2, c2, d7), (a8, b2, c2,d8), (a8, b2, c2, d9), (a8, b2, c2, d10), (a8, b2, c2, d11), (a8, b2,c2, d12), (a8, b2, c2, d13), (a8, b2, c2, d14), (a8, b2, c2, d15), (a8,b2, c2, d16), (a8, b2, c2, d17), (a8, b2, c2, d18), (a8, b2, c2, d19),(a8, b2, c2, d20), (a8, b2, c2, d21), (a8, b2, c2, d22), (a8, b2, c3,d1), (a8, b2, c3, d2), (a8, b2, c3, d3), (a8, b2, c3, d4), (a8, b2, c3,d5), (a8, b2, c3, d6), (a8, b2, c3, d7), (a8, b2, c3, d8), (a8, b2, c3,d9), (a8, b2, c3, d10), (a8, b2, c3, d11), (a8, b2, c3, d12), (a8, b2,c3, d13), (a8, b2, c3, d14), (a8, b2, c3, d15), (a8, b2, c3, d16), (a8,b2, c3, d17), (a8, b2, c3, d18), (a8, b2, c3, d19), (a8, b2, c3, d20),(a8, b2, c3, d21), (a8, b2, c3, d22), (a8, b3, c1, d1), (a8, b3, c1,d2), (a8, b3, c1, d3), (a8, b3, c1, d4), (a8, b3, c1, d5), (a8, b3, c1,d6), (a8, b3, c1, d7), (a8, b3, c1, d8), (a8, b3, c1, d9), (a8, b3, c1,d10), (a8, b3, c1, d11), (a8, b3, c1, d12), (a8, b3, c1, d13), (a8, b3,c1, d14), (a8, b3, c1, d15), (a8, b3, c1, d16), (a8, b3, c1, d17), (a8,b3, c1, d18), (a8, b3, c1, d19), (a8, b3, c1, d20), (a8, b3, c1, d21),(a8, b3, c1, d22), (a8, b3, c2, d1), (a8, b3, c2, d2), (a8, b3, c2, d3),(a8, b3, c2, d4), (a8, b3, c2, d5), (a8, b3, c2, d6), (a8, b3, c2, d7),(a8, b3, c2, d8), (a8, b3, c2, d9), (a8, b3, c2, d10), (a8, b3, c2,d11), (a8, b3, c2, d12), (a8, b3, c2, d13), (a8, b3, c2, d14), (a8, b3,c2, d15), (a8, b3, c2, d16), (a8, b3, c2, d17), (a8, b3, c2, d18), (a8,b3, c2, d19), (a8, b3, c2, d20), (a8, b3, c2, d21), (a8, b3, c2, d22),(a8, b3, c3, d1), (a8, b3, c3, d2), (a8, b3, c3, d3), (a8, b3, c3, d4),(a8, b3, c3, d5), (a8, b3, c3, d6), (a8, b3, c3, d7), (a8, b3, c3, d8),(a8, b3, c3, d9), (a3, b3, c3, d10), (a8, b3, c3, d11), (a8, b3, c3,d12), (a8, b3, c3, d13), (a3, b3, c3, d14), (a8, b3, c3, d15), (a8, b3,c3, d16), (a8, b3, c3, d17), (a8, b3, c3, d18), (a8, b3, c3, d19), (a8,b3, c3, d20), (a8, b3, c3, d21), (a8, b3, c3, d22), (a3, b4, c1, d1),(a8, b4, c1, d2), (a8, b4, c1, d3), (a8, b4, c1, d4), (a8, b4, c1, d5),(a8, b4, c1, d6), (a8, b4, c1, d7), (a8, b4, c1, d8), (a8, b4, c1, d9),(a8, b4, c1, d10), (a3, b4, c1, d11), (a8, b4, c1, d12), (a8, b4, c1,d13), (a8, b4, c1, d14), (a3, b4, c1, d15), (a8, b4, c1, d16), (a8, b4,c1, d17), (a8, b4, c1, d18), (a8, b4, c1, d19), (a8, b4, c1, d20), (a8,b4, c1, d21), (a8, b4, c1, d22), (a8, b4, c2, d1), (a8, b4, c2, d2),(a8, b4, c2, d3), (a8, b4, c2, d4), (a8, b4, c2, d5), (a8, b4, c2, d6),(a8, b4, c2, d7), (a8, b4, c2, d8), (a3, b4, c2, d9), (a8, b4, c2, d10),(a8, b4, c2, d11), (a8, b4, c2, d12), (a8, b4, c2, d13), (a8, b4, c2,d14), (a8, b4, c2, d15), (a8, b4, c2, d16), (a8, b4, c2, d17), (a8, b4,c2, d18), (a8, b4, c2, d19), (a8, b4, c2, d20), (a8, b4, c2, d21), (a8,b4, c2, d22), (a8, b4, c3, d1), (a8, b4, c3, d2), (a8, b4, c3, d3), (a8,b4, c3, d4), (a8, b4, c3, d5), (a8, b4, c3, d6), (a8, b4, c3, d7), (a8,b4, c3, d8), (a8, b4, c3, d9), (a8, b4, c3, d10), (a8, b4, c3, d11),(a8, b4, c3, d12), (a8, b4, c3, d13), (a8, b4, c3, d14), (a8, b4, c3,d15), (a8, b4, c3, d16), (a3, b4, c3, d17), (a8, b4, c3, d18), (a8, b4,c3, d19), (a8, b4, c3, d20), (a3, b4, d21), (a3, b4, c3, d22), (a8, b5,c1, d1), (a8, b5, c1, d2), (a8, b5, c1, d3), (a8, b5, c1, d4), (a8, b5,c1, d5), (a5, b5, c1, d6), (a8, b5, c1, d7), (a8, b5, c1, d8), (a8, b5,c1, d9), (a8, b5, c1, d10), (a8, b5, c1, d11), (a8, b5, c1, d12), (a3,b5, c1, d13), (a8, b5, c1, d14), (a8, b5, c1, d15), (a8, b5, c1, d16),(a8, b5, c1, d17), (a8, b5, c1, d18), (a3, b5, c1, d19), (a8, b5, c1,d20), (a8, b5, c1, d21), (a8, b5, c1, d22), (a8, b5, c2, d1), (a8, b5,c2, d2), (a8, b5, c2, d3), (a8, b5, c2, d4), (a8, b5, c2, d5), (a8, b5,c2, d6), (a8, b5, c2, d7), (a8, b5, c2, d8), (a3, b5, c2, d9), (a8, b5,c2, d10), (a8, b5, c2, d11), (a8, b5, c2, d12), (a8, b5, c2, d13), (a8,b5, c2, d14), (a8, b5, c2, d15), (a8, b5, c2, d16), (a8, b5, c2, d17),(a8, b5, c2, d18), (a8, b5, c2, d19), (a3, b5, c2, d20), (a8, b5, c2,d21), (a8, b5, c2, d22), (a8, b5, c3, d1), (a8, b5, c3, d2), (a8, b5,c3, d3), (a8, b5, c3, d4), (a8, b5, c3, d5), (a8, b5, c3, d6), (a8, b5,c3, d7), (a8, b5, c3, d8), (a8, b5, c3, d9), (a3, b5, c3, d10), (a5, b5,c3, d11), (a8, b5, c3, d12), (a3, b5, c3, d13), (a8, b5, c3, d14), (a8,b5, c3, d15), (a8, b5, c3, d16), (a8, b5, c3, d17), (a8, b5, c3, d18),(a8, b5, c3, d19), (a8, b5, c3, d20), (a8, b5, c3, d21), (a8, b5, c3,d22), (a8, b6, c1, d1), (a8, b6, c1, d2), (a8, b6, c1, d3), (a8, b6, c1,d4), (a8, b6, c1, d5), (a8, b6, c1, d6), (a8, b6, c1, d7), (a8, b6, c1,d8), (a8, b6, c1, d9), (a8, b6, c1, d10), (a8, b6, c1, d11), (a8, b6,c1, d12), (a8, b6, c1, d13), (a3, b6, c1, d14), (a8, b6, c1, d15), (a8,b6, c1, d16), (a8, b6, c1, d17), (a8, b6, c1, d18), (a8, b6, c1, d19),(a3, b6, c1, d20), (a8, b6, c1, d21), (a8, b6, c1, d22), (a8, b6, c2,d1), (a8, b6, c2, d2), (a8, b6, c2, d3), (a8, b6, c2, d4), (a8, b6, c2,d5), (a8, b6, c2, d6), (a3, b6, c2, d7), (a8, b6, c2, d8), (a8, b6, c2,d9), (a8, b6, c2, d19), (a8, b6, c2, d11), (a8, b6, c2, d12), (a8, b6,c2, d13), (a8, b6, c2, d14), (a8, b6, c2, d15), (a8, b6, c2, d16), (a8,b6, c2, d17), (a8, b6, c2, d18), (a8, b6, c2, d19), (a3, b6, c2, d20),(a8, b6, c2, d21), (a8, b6, c2, d22), (a8, b6, c3, d1), (a8, b6, c3,d2), (a3, b6, c3, d3), (a8, b6, c3, d4), (a8, b6, c3, d5), (a8, b6, c3,d6), (a8, b6, c3, d7), (a3, b6, c3, d8), (a8, b6, c3, d9), (a8, b6, c3,d10), (a8, b7, c3, d11), (a8, b6, c3, d12), (a8, b6, c3, d13), (a8, b6,c3, d14), (a8, b6, c3, d15), (a8, b6, c3, d16), (a8, b6, c3, d17), (a8,b6, c3, d18), (a8, b6, c3, d19), (a3, b6, c3, d20), (a8, b6, c3, d21),(a3, b6, c3, d22), (a9, b1, c1, d1), (a9, b1, c1, d2), (a9, b1, c1, d3),(a9, b1, c1, d4), (a9, b1, c1, d5), (a9, b1, c1, d6), (a9, b1, c1, d7),(a9, b1, c1, d8), (a9, b1, c1, d9), (a9, b1, c1, d10), (a9, b1, c1,d11), (a9, b1, c1, d12), (a9, b1, c1, d13), (a9, b1, c1, d14), (a9, b1,c1, d15), (a9, b1, c1, d16), (a9, b1, c1, d17), (a9, b1, c1, d18), (a9,b1, c1, d19), (a9, b1, c1, d20), (a9, b1, c1, d21), (a9, b1, c1, d22),(a9, b1, c2, d1), (a9, b1, c2, d2), (a9, b1, c2, d3), (a9, b1, c2, d4),(a9, b1, c2, d5), (a9, b1, c2, d6), (a9, b1, c2, d7), (a9, b1, c2, d8),(a9, b1, c2, d9), (a9, b1, c2, d10), (a9, b1, c2, d11), (a9, (a9, c2,d12), (a9, b1, c2, d13), (a9, b1, c2, d14), (a9, b1, c2, d15), (a9, b1,c2, d16), (a9, b1, c2, d17), (a9, b1, c2, d18), (a9, b1, c2, d19), (a9,b1, c2, d20), (a9, b1, c2, d21), (a9, b1, c2, d22), (a9, b1, c3, d1),(a9, b1, c3, d2), (a9, b1, c3, d3), (a9, b1, c3, d4), (a9, b1, c3, d5),(a9, b1, c3, d6), (a9, b1, c3, d7), (a9, b1, c3, d8), (a9, b1, c3, d9),(a9, b1, c3, d10), (a9, b1, c3, d11), (a9, b1, c3, d12), (a9, b1, c3,d13), (a9, b1, c3, d14), (a9, b1, c3, d15), (a9, b1, c3, d16), (a9, b1,c3, d17), (a9, b1, c3, d18), (a9, b1, c3, d19), (a9, b1, c3, d20), (a9,b1, c3, d21), (a9, b1, c3, d22), (a9, b2, c1, d1), (a9, b2, c1, d2),(a9, b2, c1, d3), (a9, b2, c1, d4), (a9, b2, c1, d5), (a9, b2, c1, d6),(a9, b2, c1, d7), (a9, b2, c1, d8), (a9, b2, c1, d9), (a9, b2, c1, d10),(a9, b2, c1, d11), (a9, b2, c1, d12), (a9, b2, c1, d13), (a9, b2, c1,d14), (a9, b2, c1, d15), (a9, b2, c1, d16), (a9, b2, c1, d17), (a9, b2,c1, d18), (a9, b2, c1, d19), (a9, b2, c1, d20), (a9, b2, c1, d21), (a9,b2, c1, d22), (a9, b2, c2, d1), (a9, b2, c2, d2), (a9, b2, c2, d3), (a9,b2, c2, d4), (a9, b2, c2, d5), (a9, b2, c2, d6), (a9, b2, c2, d7), (a9,b2, c2, d8), (a9, b2, c2, d9), (a9, b2, c2, d10), (a9, b2, c2, d11),(a9, b2, c2, d12), (a9, b2, c2, d13), (a9, b2, c2, d14), (a9, b2, c2,d15), (a9, b2, c2, d16), (a9, b2, c2, d17), (a9, b2, c2, d18), (a9, b2,c2, d19), (a9, b2, c2, d20), (a9, b2, c2, d21), (a9, b2, c2, d22), (a9,b2, c3, d1), (a9, b2, c3, d2), (a9, b2, c3, d3), (a9, b2, c3, d4), (a9,b2, c3, d5), (a9, b2, c3, d6), (a9, b2, c3, d7), (a9, b2, c3, d8), (a9,b2, c3, d9), (a9, b2, c3, d10), (a9, b2, c3, d11), (a9, b2, c3, d12),(a9, b2, c3, d13), (a9, b2, c3, d14), (a9, b2, c3, d15), (a9, b2, c3,d16), (a9, b2, c3, d17), (a9, b2, c3, d18), (a9, b2, c3, d19), (a9, b2,c3, d20), (a9, b2, c3, d21), (a9, b2, c3, d22), (a9, b3, c1, d1), (a9,b3, c1, d2), (a9, b3, c1, d3), (a9, b3, c1, d4), (a9, b3, c1, d5), (a9,b3, c1, d6), (a9, b3, c1, d7), (a9, b3, c1, d8), (a9, b3, c1, d9), (a9,b3, c1, d10), (a9, b3, c1, d11), (a9, b3, c1, d12), (a9, b3, c1, d13),(a9, b3, c1, d14), (a9, b3, c1, d15), (a9, b3, c1, d16), (a9, b3, c1,d17), (a9, b3, c1, d18), (a9, b3, c1, d19), (a9, b3, c1, d20), (a9, b3,c1, d21), (a9, b3, c1, d22), (a9, b3, c2, d1), (a9, b3, c2, d2), (a9,b3, c2, d3), (a9, b3, c2, d4), (a9, b3, c2, d5), (a9, b3, c2, d6), (a9,b3, c2, d7), (a9, b3, c2, d8), (a9, b3, c2, d9), (a9, b3, c2, d10), (a9,b3, c2, d11), (a9, b3, c2, d12), (a9, b3, c2, d13), (a9, b3, c2, d14),(a9, b3, c2, d15), (a9, b3, c2, d16), (a9, b3, c2, d17), (a9, b3, c2,d18), (a9, b3, c2, d19), (a9, b3, c2, d20), (a9, b3, c2, d21), (a9, b3,c2, d22), (a9, b3, c3, d1), (a9, b3, c3, d2), (a9, b3, c3, d3), (a9, b3,c3, d4), (a9, b3, c3, d5), (a9, b3, c3, d6), (a9, b3, c3, d7), (a9, b3,c3, d8), (a9, b3, c3, d9), (a9, b3, c3, d10), (a9, b3, c3, d11), (a9,b3, c3, d12), (a9, b3, c3, d13), (a9, b3, c3, d14), (a9, b3, c3, d15),(a9, b3, c3, d16), (a9, b3, c3, d17), (a9, b3, c3, d18), (a9, b3, c3,d19), (a9, b3, c3, d20), (a9, b3, c3, d21), (a9, b3, c3, d22), (a9, b4,c1, d1), (a9, b4, c1, d2), (a9, b4, c1, d3), (a9, b4, c1, d4), (a9, b4,c1, d5), (a9, b4, c1, d6), (a9, b4, c1, d7), (a9, b4, c1, d8), (a9, b4,c1, d9), (a9, b4, c1, d10), (a9, b4, c1, d11), (a9, b4, c1, d12), (a9,b4, c1, d13), (a9, b4, c1, d14), (a9, b4, c1, d15), (a9, b4, c1, d16),(a9, b4, c1, d17), (a9, b4, c1, d18), (a9, b4, c1, d19), (a9, b4, c1,d20), (a9, b4, c1, d21), (a9, b4, c1, d22), (a9, b4, c2, d1), (a9, b4,c2, d2), (a9, b4, c2, d3), (a9, b4, c2, d4), (a9, b4, c2, d5), (a9, b4,c2, d6), (a9, b4, c2, d7), (a9, b4, c2, d8), (a9, b4, c2, d9), (a9, b4,c2, d10), (a9, b4, c2, d11), (a9, b4, c2, d12), (a9, b4, c2, d13), (a9,b4, c2, d14), (a9, b4, c2, d15), (a9, b4, c2, d16), (a9, b4, c2, d17),(a9, b4, c2, d18), (a9, b4, c2, d19), (a9, b4, c2, d20), (a9, b4, c2,d21), (a9, b4, c2, d22), (a9, b4, c3, d1), (a9, b4, c3, d2), (a9, b4,c3, d3), (a9, b4, c3, d4), (a9, b4, c3, d5), (a9, b4, c3, d6), (a9, b4,c3, d7), (a9, b4, c3, d8), (a9, b4, c3, d9), (a9, b4, c3, d10), (a9, b4,c3, d11), (a9, b4, c3, d12), (a9, b4, c3, d13), (a9, b4, c3, d14), (a9,b4, c3, d15), (a9, b4, c3, d16), (a9, b4, c3, d17), (a9, b4, c3, d18),(a9, b4, c3, d19), (a9, b4, c3, d20), (a9, b4, c3, d21), (a9, b4, c3,d22), (a9, b5, c1, d1), (a9, b6, c1, d2), (a9, b5, c1, d3), (a9, b5, c1,d4), (a9, b5, c1, d5), (a9, b5, c1, d6), (a9, b5, c1, d7), (a9, b5, c1,d8), (a9, b5, c1, d9), (a9, b5, c1, d10), (a9, b5, c1, d11), (a9, b5,c1, d12), (a9, b5, c1, d13), (a9, b5, c1, d14), (a9, b5, c1, d15), (a9,b5, c1, d16), (a9, b5, c1, d17), (a9, b5, c1, d18), (a9, b5, c1, d19),(a9, b5, c1, d20), (a9, b5, c1, d21), (a9, b5, c1, d22), (a9, b5, c2,d1), (a9, b5, c2, d2), (a9, b5, c2, d3), (a9, b5, c2, d4), (a9, b5, c2,d5), (a9, b5, c2, d6), (a9, b5, c2, d7), (a9, b5, c2, d8), (a9, b5, c2,d9), (a9, b5, c2, d10), (a9, b5, c2, d11), (a9, b5, c2, d12), (a9, b5,c2, d13), (a9, b5, c2, d14), (a9, b5, c2, d15), (a9, b5, c2, d16), (a9,b5, c2, d17), (a9, b5, c2, d18), (a9, b5, c2, d19), (a9, b5, c2, d20),(a9, b5, c2, d21), (a9, b5, c2, d22), (a9, b5, c3, d1), (a9, b5, c3,d2), (a9, b5, c3, d3), (a9, b5, c3, d4), (a9, b5, c3, d5), (a9, b9, c3,d6), (a9, b5, c3, d7), (a9, b5, c3, d8), (a9, b5, c3, d9), (a9, b5, c3,d10), (a9, b5, c3, d11), (a9, b9, c3, d12), (a9, b5, c3, d13), (a9, b5,c3, d14), (a9, b5, c3, d15), (a9, b5, c3, d16), (a9, b5, c3, d17), (a9,b5, c3, 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d19), (a13,b3, c3, d20), (a13, b3, c1, d21), (a13, b3, c3, d22), (a13, b4, c1, d1),(a13, b4, c1, d2), (a13, b4, c1, d3), (a13, b4, c1, d4), (a13, b4, c1,d5), (a13, b4, c1, d6), (a13, b4, c1, d7), (a13, b4, c1, d8), (a13, b4,c1, d9), (a13, b4, c1, d10), (a13, b4, c1, d11), (a13, b4, c1, d12),(a13, b4, c1, d13), (a13, b4, c1, d14), (a13, b4, c1, d15), (a13, b4,c1, d16), (a13, b4, c1, d17), (a13, b4, c1, d18), (a13, b4, c1, d19)(a13, b4, c1, d20), (a13, b4, c1, d21), (a13, b4, c1, d22), (a13, b4,c2, d1), (a13, b4, c2, d2), (a13, b4, c2, d3), (a13, b4, c2, d4), (a13,b4, c2, d5), (a13, b4, c2, d6), (a13, b4, c2, d7), (a13, b4, c2, d3),(a13, b4, c2, d9), (a13, b4, c2, d10), (a13, b4, c2, d11), (a13, b4, c2,d12), (a13, b4, c2, d13), (a13, b4, c2, d14), (a13, b4, c2, d15), (a13,b4, c2, d16), (a13, b4, c2, d17), (a13, b4, c2, d18), (a13, b4, c2,d19), (a13, b4, c2, d20), (a13, b4, c2, d21), (a13, b4, c2, d22), (a13,b4, c3, d1), (a13, b4, c3, d2), (a13, b4, c3, d3), (a13, b4, c3, d4),(a13, b4, c3, d5), (a13, b4, c3, d6), (a13, b4, c3, d7), (a13, b4, c3,d8), (a13, b4, c3, d9), (a13, b4, c3, d10), (a13, b4, c3, d11), (a13,b4, c3, d12), (a13, b4, c3, d13), (a13, b4, c3, d14), (a13, b4, c3,d15), (a13, b4, c3, d16), (a13, b4, c3, d17), (a13, b4, c3, d18), (a13,b4, c3, d19), (a13, b4, c3, d20), (a13, b4, c3, d21), (a13, b4, c3,d22), (a13, b5, c1, d1), (a13, b5, c1, d2), (a13, b5, c1, d3), (a13, b5,c1, d4), (a13, b5, c1, d5), (a13, b5, c1, d6), (a13, b5, c1, d7), (a13,b5, c1, d8), (a13, b5, c1, d9), (a13, b5, c1, d10), (a13, b5, c1, d11),(a13, b5, c1, d12), (a13, b5, c1, d13), (a13, b5, c1, d14), (a13, b5,c1, d15), (a13, b5, c1, d16), (a13, b5, c1, d17), (a13, b5, c1, d18),(a13, b5, c1, d19), (a13, b5, c1, d20), (a13, b5, c1, d21), (a13, b5,c1, d22), (a13, b5, c2, d1), (a13, b5, c2, d2), (a13, b5, c2, d3), (a13,b5, c2, d4), (a13, b5, c2, d5), (a13, b5, c2, d6), (a13, b5, c2, d7),(a13, b5, c2, d8), (a13, b5, c2, d9), (a13, b5, c2, d10), (a13, b5, c2,d11), (a13, b5, c2, d12), (a13, b5, c2, d13), (a13, b5, c2, d14), (a13,b5, c2, d15), (a13, b5, c2, d16), (a13, b5, c2, d17), (a13, b5, c2,d18), (a13, b5, c2, d19), (a13, b5, c2, d20), (a13, b5, c2, d21), (a13,b5, c2, d22), (a13, b5, c3, d1), (a13, b5, c3, d2), (a13, b5, c3, d3),(a13, b5, c3, d4), (a13, b5, c3, d5), (a13, b5, c3, d6), (a13, b5, c3,d7), (a13, b5, c3, d8), (a13, b5, c3, d9), (a13, b5, c3, d10), (a13, b5,c3, d11), (a13, b5, c3, d12), (a13, b5, c3, d13), (a13, b5, c3, d14),(a13, b5, c3, d15), (a13, b5, c3, d6), (a13, b5, c3, d17), (a13, b5, c3,d18), (a13, b5, c3, d19), (a13, b5, c3, d20), (a13, b5, c3, d21), (a13,b5, c3, d22), (a13, b6, c1, d1), (a13, b6, c1, d2), (a13, b6, c1, d3),(a13, b6, c1, d4), (a13, b6, c1, d5), (a13, b6, c1, d6), (a13, b6, c1,d7), (a13, b6, c1, d8), (a13, b6, c1, d9), (a13, b6, c1, d10), (a13, b6,c1, d11), (a13, b6, c1, d12), (a13, b6, c1, d13), (a13, b6, c1, d14),(a13, b6, c1, d15), (a13, b6, c1, d16), (a13, b6, c1, d17), (a13, b6,c1, d18), (a13, b6, c1, d19), (a13, b6, c1, d20), (a13, b6, c1, d21),(a13, b6, c1, d22), (a13, b6, c2, d1), (a13, b6, c2, d2), (a13, b6, c2,d3), (a13, b6, c2, d4), (a13, b6, c2, d5), (a13, b6, c2, d6), (a13, b6,c2, d7), (a13, b6, c2, d8), (a13, b6, c2, d9), (a13, b6, c2, d10), (a13,b6, c2, d11), (a13, b6, c2, d12), (a13, b6, c2, d13), (a13, b6, c2,d14), (a13, b6, c2, d15), (a13, b6, c2, d16), (a13, b6, c2, d17), (a13,b6, c2, d18), (a13, b6, c2, d19), (a13, b6, c2, d20), (a13, b6, c2,d21), (a13, b6, c2, d22), (a13, b6, c3, d1), (a13, b6, c3, d2), (a13,b6, c3, d3), (a13, b6, c3, d4), (a13, b6, c3, d5), (a13, b6, c3, d6),(a13, b6, c3, d7), (a13, b6, c3, d8), (a13, b6, c3, d9), (a13, b6, c3,d10), (a13, b6, c3, d11), (a13, b6, c3, d12), (a13, b6, c3, d13), (a13,b6, c3, d14), (a13, b6, c3, d15), (a13, b6, c3, d16), (a13, b6, c3,d17), (a13, b6, c3, d18), (a13, b6, c3, d19), (a13, b6, c3, d20), (a13,b6, c3, d21), (a13, b6, c3, d22), (a14, b1, c1, d1), (a14, b1, c1, d2),(a14, b1, c1, d3), (a14, b1, c1, d4), (a14, b1, c1, d5), (a14, b1, c1,d6), (a14, b1, c1, d7), (a14, b1, c1, d8), (a14, b1, c1, d9), (a14, b1,c1, d10), (a14, b1, c1, d11), (a14, b1, c1, d12), (a14, b1, c1, d13),(a14, b1, c1, d14), (a14, b1, c1, d15), (a14, b1, c1, d16), (a14, b1,c1, d17), (a14, b1, c1, d18), (a14, b1, c1, d19), (a14, b1, c1, d20),(a14, b1, c1, d21), (a14, b1, c1, d22), (a14, b1, c2, d1), (a14, b1, c2,d2), (a14, b1, c2, d3), (a14, b1, c2, d4), (a14, b1, c2, d5), (a14, b1,c2, d6), (a14, b1, c2, d7), (a14, b1, c2, d8), (a14, b1, c2, d9), (a14,b1, c2, d10), (a14, b1, c2, d11), (a14, b1, c2, d12), (a14, b1, c2,d13), (a14, b1, c2, d14), (a14, b1, c2, d15), (a14, b1, c2, d16), (a14,b1, c2, d17), (a14, b1, c2, d18), (a14, b1, c2, d19), (a14, b1, c2,d20), (a14, b1, c2, d21), (a14, b1, c2, d22), (a14, b1, c3, d1), (a14,b1, c3, d2), (a14, b1, c3, d3), (a14, b1, c3, d4), (a14, b1, c3, d5),(a4, b1, c3, d6), (a14, b1, c3, d7), (a14, b1, c3, d8), (a14, b1, c3,d9), (a14, b1, c3, d10), (a14, b1, c3, d11), (a14, b1, c3, d12), (a14,b1, c3, d13), (a14, b1, c3, d14), (a14, b1, c3, d15), (a14, b1, c3,d16), (a14, b1, c3, d17), (a14, b1, c3, d18), (a14, b1, c3, d19), (a14,b1, c3, d20), (a14, b1, c3, d21), (a14, b1, c3, d22), (a14, b2, c1, d1),(a14, b2, c1, d2), (a14, b2, c1, d3), (a14, b2, c1, d4), (a14, b2, c1,d5), (a14, b2, c1, d6), (a14, b2, c1, d7), (a14, b2, c1, d8), (a14, b2,c1, d9), (a14, b2, c1, d10), (a14, b2, c1, d11), (a14, b2, c1, d12),(a14, b2, c1, d13), (a14, b2, c1, d14), (a14, b2, c1, d15), (a14, b2,c1, d16), (a14, b2, c1, d17), (a14, b2, c1, d18), (a14, b2, c1, d19),(a14, b2, c1, d20), (a14, b2, c1, d21), (a14, b2, c1, d22), (a14, b2,c2, d1), (a14, b2, c2, d2), (a14, b2, c2, d3), (a14, b2, c2, d4), (a14,b2, c2, d5), (a14, b2, c2, d6), (a14, b2, c2, d7), (a14, b2, c2, d8),(a14, b2, c2, d9), (a14, b2, c2, d10), (a14, b2, c2, d11), (a14, b2, c2,d12), (a14, b2, c2, d13), (a14, b2, c2, d14), (a4, b2, c2, d15), (a14,b2, c2, d16), (a14, b2, c2, d17), (a14, b2, c2, d18), (a14, b2, c2,d19), (a14, b2, c2, d20), (a14, b2, c2, d21), (a14, b2, c2, d22), (a14,b2, c3, d1), (a14, b2, c3, d2), (a14, b2, c3, d3), (a14, b2, c3, d4),(a14, b2, c3, d5), (a14, b2, c3, d6), (a14, b2, c3, d7), (a14, b2, c3,d8), (a14, b2, c3, d9), (a14, b2, c3, d10), (a14, b2, c3, d11), (a14,b2, c3, d12), (a14, b2, c3, d13), (a14, b2, c3, d14), (a14, b2, c3,d15), (a14, b2, c3, d16), (a14, b2, c3, d17), (a14, b2, c3, d18), (a14,b2, c3, d19), (a14, b2, c3, d20), (a14, b2, c3, d21), (a14, b2, c3,d22), (a14, b3, c3, d1), (a14, b3, c1, d2), (a14, b3, c1, d5), (a14, b3,c1, d4), (a14, b3, c1, d5), (a14, b3, c1, d6), (a14, b3, c1, d7), (a14,b3, c1, d8), (a14, b3, c1, d9), (a14, b3, c1, d10), (a14, b3, c1, d11),(a14, b3, c1, d12), (a14, b3, c1, d13), (a14, b3, c1, d14), (a14, b3,c1, d15), (a14, b3, c1, d16), (a14, b3, c1, d17), (a14, b3, c1, d18),(a14, b3, c1, d19), (a14, b3, c1, d20), (a14, b3, c1, d21), (a14, b3,c1, d22), (a14, b3, c2, d1), (a14, b3, c2, d2), (a14, b3, c2, d3), (a14,b3, c2, d4), (a14, b3, c2, d5), (a14, b3, c2, d6), (a14, b3, c2, d7),(a14, b3, c2, d8), (a14, b3, c2, d9), (a14, b3, c2, d10), (a14, b3, c2,d11), (a14, b3, c2, d12), (a14, b3, c2, d13), (a14, b3, c2, d14), (a14,b3, c2, d15), (a14, b3, c2, d16), (a14, b3, c2, d17), (a14, b3, c2,d18), (a14, b3, c2, d19), (a14, b3, c2, d20), (a14, b3, c2, d21), (a14,b3, c2, d22), (a14, b3, c3, d1), (a14, b3, c3, d2), (a14, b3, c3, d3),(a14, b3, c3, d4), (a14, b3, c3, d5), (a14, b3, c3, d6), (a14, b3, c3,d7), (a14, b3, d8), (a14, b3, c3, d9), (a14, b3, c3, d10), (a14, b3, c3,d11), (a14, b3, c3, d12), (a14, b3, c3, d13), (a14, b3, c3, d14), (a14,b3, c3, d15), (a14, b3, c3, d16), (a14, b3, c3, d17), (a14, b3, c3,d18), (a14, b3, c3, d19), (a14, b3, c3, d20), (a14, b3, c3, d21), (a14,b3, c3, d22), (a14, b4, c1, d1), (a14, b4, c1, d2), (a14, b4, c1, d3),(a14, b4, c1, d4), (a14, b4, c1, d5), (a14, b4, c1, d6), (a14, b4, c1,d7), (a14, b4, c1, d8), (a14, b4, c1, d9), (a14, b4, c1, d10), (a14, b4,c1, d11), (a14, b4, c1, d12), (a14, b4, c1, d13), (a14, b4, c1, d14),(a14, b4, c1, d15), (a14, b4, c1, d16), (a14, b4, c1, d17), (a14, b4,c1, d18), (a14, b4, c1, d19) (a14, b4, c1, d20), (a14, b4, c1, d21),(a14, b4, c1, d22), (a14, b4, c2, d1), (a14, b4, c2, d2), (a14, b4, c2,d3), (a14, b4, c2, d4), (a14, b4, c2, d5), (a14, b4, c2, d6), (a14, b4,c2, d7), (a14, b4, c2, d8), (a14, b4, c2, d9), (a14, b4, c2, d10), (a14,b4, c2, d11), (a14, b4, c2, d12), (a14, b4, c2, d13), (a14, b4, c2,d14), (a14, b4, c2, d15), (a14, b4, c2, d16), (a14, b4, c2, d17), (a14,b4, c2, d18), (a14, b4, c2, d19), (a14, b4, c2, d20), (a14, b4, c2,d21), (a4, b4, c2, d22), (a14, b4, c3, d1), (a14, b4, c3, d2), (a14, b4,c3, d3), (a14, b4, c3, d4), (a14, b4, c3, d5), (a14, b4, c3, d6), (a14,b4, c3, d7), (a14, b4, c3, d8), (a14, b4, c3, d9), (a14, b4, c3, d10),(a14, b4, c3, d11), (a14, b4, c3, d12), (a14, b4, c3, d13), (a14, b4,c3, d14), (a14, b4, c3, d15), (a14, b4, c3, d16), (a14, b4, c3, d17),(a14, b4, c3, d18), (a14, b4, c3, d19), (a14, b4, c3, d20), (a14, b4,c3, d21), (a14, b4, c3, d22), (a14, b5, c1, d1), (a14, b5, c1, d2),(a14, b5, c1, d3), (a14, b5, c1, d4), (a14, b5, c1, d5), (a14, b5, c1,d6), (a14, b5, c1, d7), (a14, b5, c1, d8), (a14, b5, c1, c9), (a14, b5,c1, d10), (a14, b5, c1, d11), (a14, b5, c1, d12), (a14, b5, c1, d13),(a14, b5, c1, d14), (a14, b5, c1, d15), (a14, b5, c1, d16), (a14, b5,c1, d16), (a1, b5, c1, d17), (a14, b5, c1, d18), (a14, b5, c1, d19),(a14, b5, c1, d20) (a14, b5, c1, d21), (a14, b5, c1, d22), (a14, b5, c2,d1), (a14, b5, c2, d2), (a14, b5, c2, d3), (a14, b5, c2, d4), (a14, b5,c2, d5), (a 4, b5, c2, d6), (a14, b5, c2, d7), (a14, b5, c2, d8), (a14,b5, c2, d9), (a14, b5, c2, d10), (a14, b5, c2, d11), (a14, b5, c2, d12),(a14, b5, c2, d13) (a14, b5, c2, d14), (a14, b5, c2, d15), (a14, b5, c2,d16), (a14, b5, c2, d17), (a14, b5, c2, d18), (a4, b5, c2, d19), (a14,b5, c2, d20), (a14, b5, c2, d21), (a14, b5, c2, d22), (a14, b5, c3, d1),(a14, b5, c3, d2), (a14, b5, c3, d3), (a14, b5, c3, d4), (a14, b5, c3,d5), (a14, b5, c3, d6), (a14, b5, c3, d7), (a14, b5, c3, 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d22), (a19, b1,c1, d1), (a19, b1, c1, d2), (a19, b1, c1, d3), (a19, b1, c1, d4), (a19,b1, c1, d5), (a19, b1, c1, d6), (a19, b1, c1, d7), (a19, b1, c1, d8),(a19, b1, c1, d9), (a19, b1, c1, d10), (a19, b1, c1, d11), (a79, b1, c1,d12), (a79, b1, c1, d13), (a19, b1, c1, d14), (a19, b1, c1, d15), (a19,b1, c1, d6), (a19, b1, c1, d17), (a19, b1, c1, d18), (a19, b1, c1, d19),(a19, b1, c1, d20), (a19, b1, c1, d21), (a79, b1, c1, d22), (a79, b1,c2, d1), (a79, b1, c2, d2), (a19, b1, c2, d3), (a19, b1, c2, d4), (a19,b1, c2, d5), (a19, b1, c2, d6), (a79, b1, c2, d7), (a79, b1, c2, d8),(a19, b1, c2, d9), (a19, b1, c2, d11), (a19, b1, c2, d11), (a19, b1, c2,d12), (a19, b1, c2, d13), (a19, b1, c2, d14), (a9, b1, c2, d15), (a19,b1, c2, d16), (a19, b1, c2, d17), (a19, b1, c2, d18), (a19, b1, c2,d19), (a79, b1, c2, d20), (a19, b1, c2, d21), (a19, b1, c2, d22), (a19,b1, c3, d1), (a19, b1, c3, d2), (a19, b1, c3, d3), (a19, b1, c3, d4),(a19, b1, c3, d5), (a19, b1, c3, d6), (a19, b1, c3, d7), (a19, b1, c3,d8), (a19, b1, c3, d9), (a19, b1, c3, d10), (a19, b1, c3, d11), (a19,b1, c3, d12), (a19, b1, c3, d13), (a19, b1, c3, d14), (a19, b1, c3,d15), (a19, b1, c3, d16), (a19, b1, c3, d17), (a19, b1, c3, d18), (a19,b1, c3, d19), (a19, b1, c3, d20), (a19, b1, c3, d21), (a19, b1, c3,d22), (a19, b2, c1, d1), (a19, b2, c1, d2), (a19, b2, c1, d3), (a19, b2,c1, d4), (a19, b2, c1, d5), (a19, b2, c1, d6), (a19, b2, c1, d7), (a19,b2, c1, d8), (a19, b2, c1, d9), (a19, b2, c1, d10), (a19, b2, c1, d11),(a19, b2, c1, d12), (a19, b2, c1, d13), (a79, b2, c1, d14), (a79, b2,c1, d15), (a19, b2, c1, d16), (a19, b2, c1, d17), (a19, b2, c1, d18),(a19, b2, c1, d19), (a19, b2, c1, d20), (a19, b2, c1, d21), (a19, b2,c1, d22), (a19, b2, c2, d1), (a19, b2, c2, d2), (a19, b2, c2, d3), (a19,b2, c2, d4), (a19, b2, c2, d5), (a19, b2, c2, d6), (a9, b2, c2, d7),(a79, b2, c2, d8), (a19, b2, c2, d9), (a19, b2, c2, d10), (a19, b2, c2,d11), (a19, b2, c2, d12), (a19, b2, c2, d13), (a19, b2, c2, d14), (a19,b2, c2, d15), (a19, b2, c2, d16), (a19, b2, c2, d17), (a19, b2, c2,d18), (a9, b2, c2, d19), (a19, b2, c2, d20), (a19, b2, c2, d21), (a19,b2, c2, d22), (a19, b2, c3, d1), (a19, b2, c3, d2), (a19, b2, c3, d3),(a19, b2, c3, d4), (a79, b2, c3, d5), (a19, b2, c3, d6), (a19, b2, c3,d7), (a19, b2, c3, d8), (a19, b2, c3, d9), (a19, b2, c3, d10), (a19, b2,c3, d11), (a19, b2, c3, d12), (a19, b2, c3, d13), (a19, b2, c3, d14),(a79, b2, c3, d15), (a19, b2, c3, d16), (a19, b2, c3, d17), (a19, b2,c3, d18), (a19, b2, c3, d19), (a19, b2, c3, d20), (a19, b2, c3, d21),(a19, b2, c3, d22), (a79, b3, c1, d1), (a19, b3, c1, d2), (a9, b3, c1,d3), (a19, b3, c1, d4), (a19, b3, c1, d5), (a19, b5, c1, d6), (a19, b3,c1, d7), (a19, b3, c1, d8), (a19, b3, c1, d9), (a19, b3, c1, d10), (a19,b3, c1, d11), (a79, b3, c1, d12), (a19, b3, c3, d13), (a19, b3, c3,d14), (a19, b3, c1, d15), (a19, b3, c1, d16), (a79, b3, c1, d17), (a19,b3, c1, d18), (a19, b3, c1, d19), (a19, b3, c1, d20), (a19, b3, c1,d21), (a19, b3, c1, d22), (a19, b3, c2, d1), 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c3, d3), (a19, b5, c3, d4), (a19,b5, c3, d5), (a19, b5, c3, d6), (a19, b5, c3, d7), (a19, b5, c3, d8),(a19, b5, c3, d9), (a19, b5, c3, d10), (a19, b5, c3, d11), (a19, b5, c3,d12), (a19, b5, c3, d13), (a19, b5, c3, d14), (a19, b5, c3, d15), (a19,b5, c3, d16), (a19, b5, c3, d17), (a19, b5, c3, d18), (a19, b5, c3,d19), (a19, b5, c3, d20), (a19, b5, c3, d21), (a19, b5, c3, d22), (a19,b6, c1, d1), (a19, b6, c1, d2), (a19, b6, c1, d3), (a19, b6, c1, d4),(a19, b6, c1, d5), (a19, b6, c1, d6), (a19, b6, c1, d7), (a19, b6, c1,d5), (a19, b6, c1, d9), (a19, b6, c1, d10), (a19, b6, c1, d11), (a19,b6, c1, d12), (a39, b6, c1, d13), (a19, b6, c1, d14), (a19, b6, c1,d15), (a19, b6, c1, d16), (a19, b6, c1, d17), (a19, b6, c1, d18), (a19,b6, c1, d19), (a19, b6, c1, d20), (a19, b6, c1, d21), (a9, b6, c1, d22),(a19, b6, c2, d1), (a19, b6, c2, d2), (a19, b6, c2, d3), (a19, b6, c2,d4), (a19, b6, c2, d5), (a19, b6, c2, d6), (a19, b6, c2, d7), (a19, b6,c2, d8), (a19, b6, c2, d9), (a19, b6, c2, d10), (a19, b6, 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(a20, b1, c1, d19), (a20, b1, c1, d20), (a20, b1, c1, d21),(a20, b1, c1, d22), (a20, b1, c2, d1), (a20, b1, c2, d2), (a20, b1, c2,d3), (a20, b1, c2, d4), (a20, b1, c2, d5), (a20, b1, c2, d6), (a20, b1,c2, d7), (a20, b1, c2, d8), (a20, b1, c2, d9), (a20, b1, c2, d10), (a20,b1, c2, d11), (a20, b1, c2, d12), (a20, b1, c2, d13) (a20, b1, c2, d14),(a20, b1, c2, d15), (a20, b1, c2, d16), (a20, b1, c2, d17), (a20, b1,c2, d18), (a20, b1, c2, d19), (a20, b1, c2, d20), (a20, b1, c2, d21),(a20, b1, c2, d22), (a20, b1, c3, d1), (a20, b1, c3, d2), (a20, b1, c3,d3), (a20, b1, c3, d4), (a20, b1, c3, d5), (a20, b1, c3, d6), (a20, b1,c3, d7), (a20, b1, c3, d8), (a20, b1, c3, d9), (a20, b1, c3, d10), (a20,b1, c3, d11), (a20, b1, c3, d12), (a20, b1, c3, d13), (a20, b1, c3,d14), (a20, b1, c3, d15), (a20, b1, c3, d16), (a20, b1, c3, d17), (a20,b1, c3, d18), (a20, b1, c3, d19), (a20, b1, c3, d20), (a20, b1, c3,d21), (a20, b1, c3, d22), (a20, b2, c1, d1), (a20, b2, c1, d2), (a20,b2, c1, d3), (a20, b2, c1, d4), (a20, b2, c1, d5), (a20, b2, c1, d6),(a20, b2, c1, d7), (a20, b2, c1, d8), (a20, b2, c1, d9), (a20, b2, c1,d10), (a20, b2, c1, d11), (a20, b2, c1, d12), (a20, b2, c1, d13), (a20,b2, c1, d14), (a20, b2, c1, d15), (a20, b2, c1, d16), (a20, b2, c1,d17), (a20, b2, c1, d18), (a20, b2, c1, d19), (a20, b2, c1, d20), (a20,b2, c1, d21), (a20, b2, c1, d22), (a20, b2, c2, d1), (a20, b2, c2, d2),(a20, b2, c2, d3), (a20, b2, c2, d4), (a20, b2, c2, d5), (a20, b2, c2,d6), (a20, b2, c2, d7), (a20, b2, c2, d8), (a20, b2, c2, d9), (a20, b2,c2, d10), (a20, b2, c2, d11), (a20, b2, c2, d12), (a20, b2, c2, d13),(a20, b2, c2, d14), (a20, b2, c2, d15), (a20, b2, c2, d16), (a20, b2,c2, d17), (a20, b2, c2, d18), (a20, b2, c2, d19), (a20, b2, c2, d20),(a20, b2, c2, d21), (a20, b2, c2, d22), (a20, b2, c3, d1), (a20, b2, c3,d2), (a20, b2, c3, d3), (a20, b2, c3, d4), (a20, b2, c3, d5), (a20, b2,c3, d6), (a20, b2, c3, d7), (a20, b2, c3, d8), (a20, b2, c3, d9), (a20,b2, c3, d10), (a20, b2, c3, d11), (a20, b2, c3, d12), (a20, b2, c3,d13), (a20, b2, c3, d14), (a20, b2, c3, d15), (a20, b2, c3, d16), (a20,b2, c3, d17), (a20, b2, c3, d18), (a20, b2, c3, d19), (a20, b2, c3,d20), (a20, b2, c3, d21), (a20, b2, c3, d22), (a20, b3, c1, d1), (a20,b3, c1, d2), (a20, b3, c1, d3), (a20, b3, c1, d4), (a20, b3, c1, d5),(a20, b3, c1, d6), (a20, b3, c1, d7), (a20, b3, c1, d8), (a20, b3, c1,d9), (a20, b3, c1, d10), (a20, b3, c1, d11), (a20, b3, c1, d12), (a20,b3, c1, d13), (a20, b3, c1, d14), (a20, b3, c1, d15), (a20, b3, c1,d16), (a20, b3, c1, d17), (a20, b3, c1, d18), (a20, b3, c1, d19), (a20,b3, c1, d20), (a20, b3, c1, d21), (a20, b3, c1, d22), (a20, b3, c2, d1),(a20, b3, c2, d2), (a20, b3, c2, d3), (a20, b3, c2, d4), (a20, b3, c2,d5), (a20, b3, c2, d6), (a20, b3, c2, d7), (a20, b3, c2, d8), (a20, b3,c2, d9), (a20, b3, c2, d10), (a20, b3, c2, d11), (a20, b3, c2, d12),(a20, b3, c2, d13), (a20, b3, c2, d14), (a20, b3, c2, d15), (a20, b3,c2, d16), (a20, b3, c2, d17), (a20, b3, c2, d18), (a20, b3, c2, d19),(a20, b3, c2, d20), (a20, b3, c2, d21), (a20, b3, c2, d22), (a20, b3,c3, d1), (a20, b3, c3, d2), (a20, b3, c3, d3), (a20, b3, c3, d4), (a20,b3, c3, d5), (a20, b3, c3, d6), (a20, b3, c3, d7), (a20, b3, c3, d8),(a20, b3, c3, d9), (a20, b3, c3, d10), (a20, b3, c3, d11), (a20, b3, c3,d12), (a20, b3, c3, d13), (a20, b3, c3, d14), (a20, b3, c3, d15), (a20,b3, c3, d16), (a20, b3, c3, d11), (a20, b3, c3, d18), (a20, b3, c3,d19), (a20, b3, c3, d20), (a20, b3, c3, d21), (a20, b3, c3, d22), (a20,b4, c1, d1), (a20, b4, c1, d2), (a20, b4, c1, d3), (a20, b4, c1, d4),(a20, b4, c1, d5), (a20, b4, c1, d6), (a20, b4, c1, d7), (a20, b4, c1,d8), (a20, b4, c1, d9), (a20, b4, c1, d10), (a20, b4, c1, d11), (a20,b4, c1, d12), (a20, b4, c1, d13), (a20, b4, c1, d14), (a20, b4, c1,d15), (a20, b4, c1, d16), (a20, b4, c1, d17), (a20, b4, c1, d18), (a20,b4, c1, d10), (a20, b4, c1, d20), (a20, b4, c1, d21), (a20, b4, c1,d22), (a20, b4, c2, d1), (a20, b4, c2, d2), (a20, b4, c2, d13), (a20,b4, c2, d4), (a20, b4, c2, d5), (a20, b4, c2, d6), (a20, b4, c2, d7),(a20, b4, c2, d8), (a20, b4, c2, d9), (a20, b4, c2, d10), (a20, b4, c2,d11), (a20, b4, c2, d12), (a20, b4, c2, d13), (a20, b4, c2, d14), (a20,b4, c2, d15), (a20, b4, c2, d16), (a20, b4, c2, d17), (a20, b4, c2,d18), (a20, b4, c2, d19), (a20, b4, c2, d20), (a20, b4, c2, d21), (a20,b4, c2, d22), (a20, b4, c3, d1), (a20, b4, c3, d2), (a20, b4, c3, d3),(a20, b4, c3, d4), (a20, b4, c3, d5), (a20, b4, c3, d6), (a20, b4, c3,d7), (a20, b4, c3, d8), (a20, b4, c3, d9), (a20, b4, c3, d10), (a20, b4,c3, d11), (a20, b4, c3, d12), (a20, b4, c3, d13), (a20, b4, c3, d14),(a20, b4, c3, d15), (a20, b4, c3, d16), (a20, b4, c3, d17), (a20, b4,c3, d18), (a20, b4, c3, d19), (a20, b4, c3, d20), (a20, b4, c3, d21),(a20, b4, c3, d22), (a20, b5, c1, d1), (a20, b5, c1, d2), (a20, b5, c1,d3), (a20, b5, c1, d4), (a20, b5, c1, d5), (a20, b5, c1, d6), (a20, b5,c1, d7), (a20, b5, c1, d8), (a20, b5, c1, d9), (a20, b5, c1, d10), (a20,b5, c1, d11), (a20, b5, c1, d12), (a20, b5, c1, d13), (a20, b5, c1,d14), (a20, b5, c1, d15), (a20, b5, c1, d16), (a20, b5, c1, d17), (a20,b5, c1, d18), (a20, b5, c1, d19), (a20, b5, c1, d20), (a20, b5, c1,d21), (a20, b5, c1, d22), (a20, b5, c2, d1), (a20, b5, c2, d2), (a20,b5, c2, d3), (a20, b5, c2, d4), (a20, b5, c2, d5), (a20, b5, c2, d6),(a20, b5, c2, d7), (a20, b5, c2, d8), (a20, b5, c2, d9), (a20, b5, c2,d10), (a20, b5, c2, d11), (a20, b5, c2, d12), (a20, b5, c2, d13), (a20,b5, c2, d14), (a20, b5, c2, d15), (a20, b5, c2, d16), (a20, b5, c2,d17), (a20, b5, c2, d18), (a20, b5, c2, d19), (a20, b5, c2, d20), (a20,b5, c2, d21), (a20, b5, c2, d22), (a20, b5, c3, d1), (a20, b5, c3, d2),(a20, b5, c3, d3), (a20, b5, c3, d4), (a20, b5, c3, d5), (a20, b5, c3,d6), (a20, b5, c3, d7), (a20, b5, c3, d3), (a20, b5, c3, d9), (a20, b5,c3, d10), (a20, b5, c3, d11), (a20, b5, c3, d12), (a20, b5, c3, d13),(a20, b5, c3, d14), (a20, b5, c3, d15), (a20, b5, c3, d16), (a20, b5,c3, d17), (a20, b5, c3, d18), (a20, b5, c3, d19), (a20, b5, c3, d20),(a20, b5, c3, d21), (a20, b5, c3, d22), (a20, b6, c1, d1), (a20, b6, c1,d2), (a20, b6, c1, d3), (a20, b6, c1, d4), (a20, b6, c1, d5), (a20, b6,c1, d6), (a20, b6, c1, d7), (a20, b6, c1, d8), (a20, b6, c1, d9), (a20,b6, c1, d10), (a20, b6, c1, d11), (a20, b6, c1, d12), (a20, b6, c1,d13), (a20, b6, c1, d14), (a20, b6, c1, d15), (a20, b6, c1, d16), (a20,b6, c1, d17), (a20, b6, c1, d18), (a20, b6, c1, d19), (a20, b6, c1,d20), (a20, b6, c1, d21), (a20, b6, c1, d22), (a20, b6, c2, d1), (a20,b6, c2, d2), (a20, b6, c2, d3), (a20, b6, c2, d4), (a20, b6, c2, d5),(a20, b6, c2, d6), (a20, b6, c2, d7), (a20, b6, c2, d8), (a20, b6, c2,d9) (a20, b6, c2, d10), (a20, b6, c2, d11), (a20, b6, c2, d12), (a20,b6, c2, d13), (a20, b6, c2, d14), (a20, b6, c2, d15), (a20, b6, c2,d16), (a20, b6, c2, d17), (a20, b6, c2, d18), (a20, b6, c2, d19), (a20,b6, c2, d20), (a20, b6, c2, d21), (a20, b6, c2, d22), (a20, b6, c3, d1),(a20, b6, c3, d2), (a20, b6, c3, d3), (a20, b6, c3, d4), (a20, b6, c3,d5), (a20, b6, c3, d6), (a20, b6, c3, d7), (a20, b6, c3, d8), (a20, b6,c3, d9), (a20, b6, c3, d10), (a20, b6, c3, d11), (a20, b6, c3, d12),(a20, b6, c3, d13), (a20, b6, c3, d14), (a20, b6, c3, d15), (a20, b6,c3, d16), (a20, b6, c3, d17), (a20, b6, c3, d18), (a20, b6, c3, d19),(a20, b6, c3, d20), (a20, b6, c3, d21), (a20, b6, c3, d22), (a21, b1,c1, d1), (a21, b1, c1, d2), (a21, b1, c1, d3), (a21, b1, c1, d4), (a21,b1, c1, d5), (a21, b1, c1, d6), (a21, b1, c1, d7), (a21, b1, c1, d8),(a21, b1, c1, d9), (a21, b1, c1, d10), (a21, b1, c1, d11), (a21, b1, c1,d12), (a21, b1, c1, d13), (a21, b1, c1, d14), (a21, b1, c1, d15), (a21,b1, c1, d16), (a21, b1, c1, d17), (a21, b1, c1, d13), (a21, b1, c1,d19), (a21, b1, c1, d20), (a21, b1, c1, d21), (a21, b1, c1, d22), (a21,b1, c2, d1), (a21, b1, c2, d2), (a21, b1, c2, d3), (a21, b1, c2, d4),(a21, b1, c2, d5), (a21, b1, c2, d6), (a21, b1, c2, d7), (a21, b1, c2,d8), (a21, b1, c2, d9), (a21, b1, c2, d10), (a21, b1, c2, d11), (a21,b1, c2, d12), (a21, b1, c2, d13), (a21, b1, c2, d14), (a21, b1, c2,d15), (a21, b1, c2, d16), (a21, b1, c2, d17), (a21, b1, c2, d13), (a21,b1, c2, d19), (a21, b1, c2, d20), (a21, b1, c2, d21), (a21, b1, c2,d22), (a21, b1, c3, d1), (a21, b1, c3, d2), (a21, b1, c3, d3), (a21, b1,c3, d4), (a21, b1, c3, d5), (a21, b1, c3, d6), (a21, b1, c3, d7), (a21,b1, c3, d8), (a21, b1, c3, d9), (a21, b1, c3, d10), (a21, b1, c3, d11),(a21, b1, c3, d12), (a21, b1, c3, d13), (a21, b1, c3, d14), (a21, b1,c3, d15), (a21, b1, c3, d16), (a21, b1, c3, d17), (a21, b1, c3, d18),(a21, b1, c3, d19), (a21, b1, c3, d20), (a21, b1, c3, d21), (a21, b1,c3, d22), (a21, b2, c1, d1), (a21, b2, c1, d2), (a21, b2, c1, d3), (a21,b2, c1, d4), (a21, b2, c1, d5), (a21, b2, c1, d6), (a21, b2, c1, d7),(a21, b2, c1, d8), (a21, b2, c1, d9), (a21, b2, c1, d10), (a21, b2, c1,d11), (a21, b2, c1, d12), (a21, b2, c1, d13), (a21, b2, c1, d14), (a21,b2, c1, d15), (a21, b2, c1, d16), (a21, b2, c1, d17), (a21, b2, c1,d18), (a21, b2, c1, d19), (a21, b2, c1, d20), (a21, b2, c1, d21), (a21,b2, c1, d22), (a21, b2, c2, d1), (a21, b2, c2, d2), (a21, b2, c2, d3),(a21, b2, c2, d4), (a21, b2, c2, d5), (a21, b2, c2, d6), (a21, b2, c2,d7), (a21, b2, c2, d8), (a21, b2, c2, d9), (a21, b2, c2, d10), (a21, b2,c2, d11), (a21, b2, c2, d12), (a21, b2, c2, d13), (a21, b2, c2, d14),(a21, b2, c2, d15), b2, c2, d20), (a21, b2, c2, d21), (a21, b2, c2,d22), (a21, b2, c3, d1), (a21, b2, c3, d2), (a21, b2, c3, d3), (a21, b2,c3, d4), (a21, b2, c3, d5), (a21, b2, c3, d6), (a21, b2, c3, d7), (a21,b2, c3, d8), (a21, b2, c3, d9), (a21, b2, c3, d10), (a21, b2, c3, d11),(a21, b2, c3, d12), (a21, b2, c3, d13), (a21, b2, c3, d14), (a21, b2,c3, d15), b2, c3, d20), (a21, b2, c3, d21), (a21, b2, c3, d22), (a21,b3, c1, d1), (a21, b3, c1, d2), (a21, b3, c1, d3), (a21, b3, c1, d4),(a21, b3, c1, d5), (a21, b3, c1, d6), (a21, b3, c1, d7), (a21, b3, c1,d8), (a21, b3, c1, d9), (a21, b3, c1, d10), (a21, b3, c1, d11), (a21,b3, c1, d12), (a21, b3, c1, d13), (a21, b3, c1, d14), (a21, b3, c1,d15), (a21, b3, c1, d16), (a21, b3, c1, d17), (a21, b3, c1, d18), (a21,b3, c1, d19), (a21, b3, c1, d20), (a21, b3, c1, d21), (a21, b3, c1,d22), (a21, b3, c2, d1), (a21, b3, c2, d2), (a21, b3, c2, d3), (a21, b3,c2, d4), (a21, b3, c2, d5), (a21, b3, c2, d6), (a21, b3, c2, d7), (a21,b3, c2, d8), (a21, b3, c2, d9), (a21, b3, c2, d10), (a21, b3, c2, d11),(a21, b3, c2, d12), (a21, b3, c2, d13), (a21, b3, c2, d14), (a21, b3,c2, d15), (a21, b3, c2, d16), (a21, b3, c2, d17), (a21, b3, c2, d18),(a21, b3, c2, d19), (a21, b3, c2, d20), (a21, b3, c2, d21), (a21, b3,c2, d22), (a21, b3, c3, d1), (a21, b3, c3, d2), (a21, b3, c3, d3), (a21,b3, c3, d4), (a21, b3, c3, d5), (a21, b3, c3, d6), (a21, b3, c3, d7),(a21, b3, c3, d8), (a21, b3, c3, d9), (a21, b3, c3, d10), (a21, b3, c3,d11), (a21, b3, c3, d12), (a21, b3, c3, d13), (a21, b3, c3, d14), (a21,b3, c3, d15), (a21, b3, c3, d16), (a21, b3, c3, d17), (a21, b3, c3,d18), (a21, b3, c3, d19), (a21, b3, c3, d20), (a21, b3, c3, d21), (a21,b3, c3, d22), (a21, b4, c1, d1), (a21, b4, c1, d2), (a21, b4, c1, d3),(a21, b4, c1, d4), (a21, b4, c1, d5), (a21, b4, c1, d6), (a21, b4, c1,d7), (a21, b4, c1, d8), (a21, b4, c1, d9), (a21, b4, c1, d10), (a21, b4,c1, dl), (a21, b4, c1, d12), (a21, b4, c1, d13), (a21, b4, c1, d14),(a21, b4, c1, d15), (a21, b4, c1, d16), (a21, b4, c1, d17), (a21, b4,c1, d18), (a21, b4, c1, d19), (a21, b4, c1, d20), (a21, b4, c1, d21),(a21, b4, c1, d22), (a21, b4, c2, d1), (a21, b4, c2, d2), (a21, b4, c2,d3), (a21, b4, c2, d4), (a21, b4, c2, d5), (a21, b4, c2, d6), (a21, b4,c2, d7), (a21, b4, c2, d8), (a21, b4, c2, d9), (a21, b4, c2, d10), (a21,b4, c2, d11), (a21, b4, c2, d12), (a21, b4, c2, d13), (a21, b4, c2,d14), (a21, b4, c2, d15), (a21, b4, c2, d16), (a21, b4, c2, d7), (a21,b4, c2, d18), (a21, b4, c2, d19), (a21, b4, c2, d20), (a21, b4, c2,d21), (a21, b4, c2, d22), (a21, b4, c3, d1), (a21, b4, c3, d2), (a21,b4, c3, d3), (a21, b4, c3, d4), (a21, b4, c3, d5), (a21, b4, c3, d6),(a21, b4, c3, d7), (a21, b4, c3, d8), (a21, b4, c3, d9), (a21, b4, c3,d10), (a21, b4, c3, d11), (a21, b4, c3, d12), (a21, b4, c3, d13), (a21,b4, c3, d14), (a21, b4, c3, d15), (a21, b4, c3, d16), (a21, b4, c3,d17), (a21, b4, c3, d18), (a21, b4, c3, d19), (a21, b4, c3, d20), (a21,b4, c3, d21), (a21, b4, c3, d22), (a21, b5, c1, d1), (a21, b5, c1, d2),(a21, b5, c1, d3), (a21, b5, c1, d4), (a21, b5, c1, d5), (a21, b5, c1,d6), (a21, b5, c1, d7), (a21, b5, c1, d8), (d21, b5, c1, d9), (a21, b5,c1, d10), (a21, b5, c1, d11), (a21, b5, c1, d12), (a21, b5, c1, d13),(a21, b5, c1, d14), (a21, b5, c1, d15), (a21, b5, c1, d16), (a21, b5,c1, d17), (a21, b5, c1, d18), (a21, b5, c1, d19), (a21, b5, c1, d20),(a21, b5, c1, d21), (a21, b5, c1, d22), (a21, b5, c2, d1), (a21, b5, c2,d2), (a21, b5, c2, d3), (a21, b5, c2, d4), (a21, b5, c2, d5), (a21, b5,c2, d6), (a21, b5, c2, d7), (a21, b5, c2, d8), (a21, b5, c2, d9), (a21,b5, c2, d10), (a21, b5, c2, d11), (a21, b5, c2, d12), (a21, b5, c2,d13), (a21, b5, c2, d14), (a21, b5, c2, d15), (a21, b5, c2, d16), (a21,b5, c2, d17), (a21, b5, c2, d18), (a21, b5, c2, d19), (a21, b5, c2,d20), (a21, b5, c2, d21), (a21, b5, c2, d22), (a21, b5, c3, d1), (a21,b5, c3, d2), (a21, b5, c3, d3), (a21, b5, c3, d4), (a21, b5, c3, d5),(a21, b5, c3, d6), (a21, b5, c3, d7), (a21, b5, c3, d8), (a21, b5, c3,d9), (a21, b5, c3, d10), (a21, b5, c3, d11); (a21, b5, c3, d12), (a21,b5, c3, d13), (a21, b5, c3, d14), (a21, b5, c3, d15), (a21, b5, c3, d16,(a21, b5, c3, d17), (a21, b5, c3, d18), (a21, b5, c3, d19), (a21, b5,c3, d20), (a21, b5, c3, d21), (a21, b5, c3, d22), (a21, b6, c1, d1),(a21, b6, c1, d2), (a21, b6, c1, d3), (a21, b6, c1, d4), (a21, b6, c1,d5), (a21, b6, c1, d6), (a21, b6, c1, d7), (a21, b6, c1, d8), (a21, b6,c1, d9), (a21, b6, c1, d10), (a21, b6, c1, d11), (a21, b6, c1, d12),(a21, b6, c1, d13), (a21, b6, c1, d14), (a21, b6, c1, d15), (a21, b6,c1, d16), (a21, b6, c1, d17), (a21, b6, c1, d18), (a21, b6, c1, d19),(a21, b6, c1, d20), (a21, b6, c1, d21), (a21, b6, c1, d22), (a21, b6,c2, d1), (a21, b6, c2, d2), (a21, b6, c2, d3), (a21, b6, c2, d4), (a21,b6, c2, d5), (a21, b6, c2, d6), (a21, b6, c2, d7), (a21, b6, c2, d8),(a21, b6, c2, d9), (a21, b6, c2, d10), (a21, b6, c2, d11), (a21, b6, c2,d12), (a21, b6, c2, d13), (a21, b6, c2, d14), (a21, b6, c2, d15), (a21,b6, c2, d16), (a21, b6, c2, d17), (a21, b6, c2, d18), (a21, b6, c2,d19), (a21, b6, c2, d20), (a21, b6, c2, d21), (a21, b6, c2, d22), (a21,b6, c3, d1), (a21, b6, c3, d2), (a21, b6, c3, d3), (a21, b6, c3, d4),(a21, b6, c3, d5), (a21, b6, c3, d6), (a21, b6, c3, d7), (a21, b6, c3,d8), (a21, b6, c3, d9), (a21, b6, c3, d10), (a21, b6, c3, d11), (a21,b6, c3, d12), (a21, b6, c3, d13), (a21, b6, c3, d14), (a21, b6, c3,d15), (a21, b6, c3, d16), (a21, b6, c3, d17), (a21, b6, c3, d18), (a21,b6, c3, d19), (a21, b6, c3, d20), (a21, b6, c3, d21), (a21, b6, c3,d22), (a22, b1, (c1, d1), (a22, b1, c1, d2), (a22, b1, c1, d3), (a22,b1, c1, d4), (a22, b1, c1, d5), (a22, b1, c1, d6), (a22, b1, c1, d7),(a22, b1, c1, d8), (a22, b1, c1, d9), (a22, b1, c1, d10), (a22, b1, c1,d11), (a22, b1, c1, d12), (a22, b1, c1, d13), (a22, b1, c1, d14), (a22,b1, c1, d15), (a22, b1, c1, d16), (a22, b1, c1, d17), (a22, b1, c1,d18), (a22, b1, c1, d19), (a22, b1, c1, d20), (a22, b1, c1, d21), (a22,b1, c1, d22), (a22, b1, c2, d1), (a22, b1, c2, d2), (a22, b1, c2, d3),(a22, b1, c2, d4), (a22, b1, c2, d5), (a22, b1, c2, d6), (a22, b1, c2,d7), (a22, b1, c2, d8), (a22, b1, c2, d9), (a22, b1, c2, d10), (a22, b1,c2, d11), (a22, b1, c2, d12), (a22, b1, c2, d13), (a22, b1, c2, d14),(a22, b1, c2, d15), (a22, b1, c2, d16), (a22, b1, c2, d17), (a22, b1,c2, d18), (a22, b1, c2, d19), (a22, b1, c2, b20), (a22, b1, c2, d21),(a22, b1, c2, d22), (a22, b1, c3, d1), (a22, b1, c3, d2), (a22, b1, c3,d3), (a22, b1, c3, d4), (a22, b1, c3, d5), (a22, b1, c3, d6), (a22, b1,c3, d7), (a22, b1, c3, d8), (a22, b1, c3, d9), (a22, b1, c3, d10), (a22,b1, c3, d11), (a22, b1, c3, d12), (a22, b1, c3, d13), (a22, b1, c3,d14), (a22, b1, c3, d15), (a22, b1, c3, d16), (a22, b1, c3, d17), (a22,b1, c3, d18), (a22, b1, c3, d19), (a22, b1, c3, d20), (a22, b1, c3,d21), (a22, b1, c3, d22), (a22, b2, c1, d1), (a22, b2, c1, d2), (a22,b2, c1, d3), (a22, b2, c1, d4), (a22, b2, c1, d5), (a22, b2, c1, d6),(a22, b2, c1, d7), (a22, b2, c1, d8), (a22, b2, c1, d9), (a22, b2, c1,d19), (a22, b2, c1, d11), (a22, b2, c1, d12), (a22, b2, c1, d13), (a22,b2, c1, d14), (a22, b2, c1, d15), (a22, b2, c1, d16), (a22, b2, c1,d17), (a22, b2, c1, d18), (a22, b2, c1, d19), (a22, b2, c1, d20), (a22,b2, c1, d21), (a22, b2, c1, d22), (a22, b2, c2, d1), (a22, b2, c2, d2),(a22, b2, c2, d3), (a22, b2, c2, d4), (a22, b2, c2, d5), (a22, b2, c2,d6), (a22, b2, c2, d7), (a22, b2, c2, d8), (a22, b2, c2, d9), (a22, b2,c2, d10), (a22, b2, c2, d11), (a22, b2, c2, d12), (a22, b2, c2, d13),(a22, b2, c2, d14), (a22, b2, c2, d15), (a22, b2, c2, d16), (a22, b2,c2, d17), (a22, b2, c2, d18), (a22, b2, c2, d19), (a22, b2, c2, d20),(a22, b2, c2, d21), (a22, b2, c2, d22), (a22, b2, c3, d1), (a22, b2, c3,d2), (a22, b2, c3, d3), (a22, b2, c3, 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(a22, b4, c1, d20), (a22, b4, c1, d21), (a22, b4, c1,d22), (a22, b4, c2, d1), (a22, b4, c2, d2), (a22, b4, c2, d3), (a22, b4,c2, d4), (a22, b4, c2, d5), (a22, b4, c2, d6), (a22, b4, c2, d7), (a22,b4, c2, d8), (a22, b4, c2, d9), (a22, b4, c2, d10), (a22, b4, c2, d11),(a22, b4, c2, d12), (a22, b4, c2, d13), (a22, b4, c2, d14), (a22, b4,c2, d15), (a22, b4, c2, d16), (a22, b4, c2, d17), (a22, b4, c2, d18),(a22, b4, c2, d19), (a22, b4, c2, d20), (a22, b4, c2, d21), (a22, b4,c2, d22), (a22, b4, c3, d1), (a22, b4, c3, d2), (a22, b4, c3, d3), (a22,b4, c3, d4), (a22, b4, c3, d5), (a22, b4, c3, d6), (a22, b4, c3, d7),(a22, b4, c3, d8), (a22, b4, c3, d9), (a22, b4, c3, d10), (a22, b4, c3,d11), (a22, b4, c3, d12), (a22, b4, c3, d13), (a22, b4, c3, d14), (a22,b4, c3, d15), (a22, b4, c3, d16), (a22, b4, c3, d17), (a22, b4, c3,d18), (a22, b4, c3, d19), (a22, b4, c3, d20), (a22, b4, c3, d21), (a22,b4, c3, d22), (a22, b5, c1, d1), (a22, b5, c1, d2), (a22, b5, c1, d3),(a22, b5, c1, d4), (a22, b5, c1, d5), (a22, b5, c1, d6), (a22, b5, c1,d7), (a22, b5, c1, d8), (a22, b5, c1, d9), (a22, b5, c1, d10), (a22, b5,c1, d11), (a22, b5, c1, d12), (a22, b5, c1, d13), (a22, b5, c1, d14),(a22, b5, c1, d15), (a22, b5, c1), (a22, b5, c1, d17), (a22, b5, c1,d18), (a22, b5, c1, d19), (a22, b5, c1, d20), (a22, b5, c1, d21), (a22,b5, c1, d22), (a22, b5, c2, d1), (a22, b5, c2, d2), (a22, b5, c2, d3),(a22, b5, c2, d4), (a22, b5, c2, d5), (a22, b5, c2, d6), (a22, b5, c2,d7), (a22, b5, c2, d8), (a22, b5, c2, d9), (a22, b5, c2, d10), (a22, b5,c2, d11), (a22, b5, c2, d12), (a22, b5, c2, d13), (a22, b5, c2, d14),(a22, b5, c2, d15), (a22, b5, c2, d16), (a22, b5, c2, d17), (a22, b5,c2, d18), (a22, b5, c2, d19), (a22, b5, c2, d20), (a22, b5, c2, d21),(a22, b5, c2, d22), (a22, b5, c3, d11), (a22, b5, c3, d2), (a22, b5, c3,d3), (a22, b5, c3, d4), (a22, b5, c3, d5), (a22, b5, c3, d6), (a22, b5,c3, d7), (a22, b5, c3, d8), (a22, b5, c3, d9), (a22, b5, c3, d10), (a22,b5, c3, d11), (a22, b5, c3, d12), (a22, b5, c3, d13), (a22, b5, c3,d14), (a22, b5, c3, d15), (a22, b5, c3, d16), (a22, b5, c3, d17), (a22,b5, c3, d18), (a22, b5, c3, d19), (a22, b5, c3, d20), (a22, b5, c3,d21), (a22, b5, c3, d22), (a22, b6, c1, d1), (a22, b6, c1, d2), (a22,b6, c1, d3), (a22, b6, c1, d4), (a22, b6, c1, d5), (a22, b6, c1, d6),(a22, b6, c1, d7), (a22, b6, c1, d8), (a22, b6, c1, d9), (a22, b6, c1,d10), (a22, b6, c1, d11), (a22, b6, c1, d12), (a22, b6, c1, d13), (a22,b6, c1, d14) (a22, b6, c1, d15), (a22, b6, c1, d16), (a22, b6, c1, d17),(a22, b6, c1, d18), (a22, b6, c1, d19), (a22, b6, c1, d20), (a22, b6,c1, d21), (a22, b6, c1, d22), (a22, b6, c2, d1), (a22, b6, c2, d2),(a22, b6, c2, d3), (a22, b6, c2, d4), (a22, b6, c2, d5), (a22, b6, c2,d6), (a22, b6, c2, d7), (a22, b6, c2, d8), (a22, b6, c2, d9), (a22, b6,c2, d6), (a22, b6, c2, d11), (a22, b6, c2, d12), (a22, b6, c2, d13),(a22, b6, c2, d14), (a22, b6, c2, d15), (a22, b6, c2, d16), (a22, b6,c2, d17), (a22, b6, c2, d18), (a22, b6, c2, d19), (a22, b6, c2, d20),(a22, b6, c2, d21), (a22, b6, c2, d22), (a22, b6, c3, d1), (a22, b6, c3,(d2), (a22, b6, c3, d3), (a22, b6, c3, d4), (a22, b6, c3, d5), (a22, b6,c3, d6), (a22, b6, c3, d7), (a22, b6, c3, d8), (a22, b6, c3, d9), (a22,b6, c3, d10), (a22, b6, c3, d11), (a22, b6, c3, d12), (a22, b6, c3,d13), (a22, b6, c3, d14), (a22, b6, c3, d15), (a22, b6, c3, d16), (a22,b6, c3, d17), (a22, b6, c3, d18), (a22, b6, c3, d19), (a22, b6, c3,d20), (a22, b6, c3, d21), (a22, b6, c3, d22), (a23, b1, c1, d1), (a23,b1, c1, d2), (a23, b1, c1, d3), (a23, b1, c1, d4), (a23, b1, c1, d5),(a23, b1, c1, d6), (a23, b1, c1, d7), (a23, b1, c1, d8), (a23, b1, c1,d9), (a23, b1, c1, d10), (a23, b1, c1, d11), (a23, b1, c1, d12), (a23,b1, b1, c1, d13), (a23, b1, c1, d14), (a23, b1, c1, d15), (a23, b1, c1,d16), (a23, b1, c1, d17), (a23, b1, c1, d18), (a23, b1, c1, d19), (a23,b1, c1, d20), (a23, b1, c1, d21), (a23, b1, c1, d22), (a23, b1, c2, d1),(a23, b1, c2, d2), (a23, b1, c2, d3), (a23, b1, c2, d4), (a23, b1, c2,d5), (a23, b1, c2, d6), (a23, b1, c2, d7), (a23, b1, c2, d8), (a23, b1,c2, d9), (a23, b1, c2, d10), (a23, b1, c2, d11), (a23, b1, c2, d12),(a23, b1, c2, d13), (a23, b1, c2, d14), (a23, b1, c2, d15), (a23, b1,c2, d16), (a23, b1, c2, d17), (a23, b1, c2, d8), (a23, b1, c2, d19),(a23, b1, c2, d20), (a23, b1, c2, d21), (a23, b1, c2, d22), (a23, b1,c3, d1), (a23, b1, c3, d2), (a23, b1, c3, d3), (a23, b1, c3, d4), (a23,b1, c3, d5), (a23, b1, c3, d6), (a23, b1, c3, d7), (a23, b1, c3, d8),(a23, b1, c3, d9), (a23, b1, c3, d10), (a23, b1, c3, d11), (a23, b1, c3,d12), (a23, b1, c3, d13), (a23, b1, c3, d14), (a23, b1, c3, d15), (a23,b1, c3, d16), (a23, b1, c3, d17), (a23, b1, c3, d18), (a23, b1, c3,d19), (a23, b1, c3, d20), (a23, b1, c3, d21), (a23, b1, c3, d22), (a23,b2, c1, d1), (a23, b2, c1, d2), (a23, b2, c1, d3), (a23, b2, c1, d4),(a23, b2, c3, d5), (a23, b2, c1, d6), (a23, b2, c1, d7), (a23, b2, c1,d8), (a23, b2, c1, d9), (a23, b2, c1, d10), (a23, b2, c1, d11), (a23,b2, c1, d12), (a23, b2, c1, d13), (a23, b2, c1, d14), (a23, b2, c1,d15), (a23, b2, c1, d16), (a23, b2, c1, d17), (a23, b2, c1, d18), (a23,b2, c1, d19), (a23, b2, c1, d20), (a23, b2, c1, d21), (a23, b2, c1,d22), (a23, b2, c2, d1), (a23, b2, c2, d2), (a23, b2, c2, d3), (a23, b2,c2, d4), (a23, b2, c2, d5), (a23, b2, c2, d6), (a23, b2, c2, d7), (a23,b2, c2, d8), (a23, b2, c2, d9), (a23, b2, c2, d10), (a23, b2, c2, d11),(a23, b2, c2, d12), (a23, b2, c2, d13), (a23, b2, c2, d14), (a23, b2,c2, d15), (a23, b2, c2, d16), (a23, b2, c2, d17), (a23, b2, c2, d18),(a23, b2, c2, d19), (a23, b2, c2, d20), (a23, b2, c2, d21), (a23, b2,c2, d22), (a23, b2, c3, d1), (a23, b2, c3, d2), (a23, b2, c3, d3), (a23,b2, c3, d4), (a23, b2, c3, d5), (a23, b2, c3, d6), (a23, b2, c3, d7),(a23, b2, c3, d8), (a23, b2, c3, d9), (a23, b2, c3, d10), (a23, b2, c3,d11), (a23, b2, c3, d12), (a23, b2, c3, d13), (a23, b2, c3, d14), (a23,b2, c3, d15), (a23, b2, c3, d16), (a23, b2, c3, d17), (a23, b2, c3,d18), (a23, b2, c3, d19), (a23, b2, c3, d20), (a23, b2, c3, d21), (a23,b2, c3, d22), (a23, b3, c1, d1), (a23, b3, c1, d2), (a23, b3, c1, d3),(a23, b3, c1, d4), (a23, b3, c1, d5), (a23, b3, c1, d6), (a23, b3, c1,d7), (a23, b3, c1, d8), (a23, b3, c1, d9), (a23, b3, c1, die), (a23, b3,c1, d11), (a23, b3, c1, d12), (a23, b3, c1, d13), (a23, b3, c1, d14),(a23, b3, c1, d15), (a23, b3, c1, d16), (a23, b3, c1, d17), (a23, b3,c1, d18), (a23, b3, c1, d19), (a23, b3, c1, d20), (a23, b3, c1, d21),(a23, b3, c1, d22), (a23, b5, c2, d1), (a23, b3, c2, d2), (a23, b3, c2,d3), (a23, b3, c2, d4), (a23, b3, c2, d5), (a23, b3, c2, d6), (a23, b3,c2, d7), (a23, b3, c2, d8), (a23, b3, c2, d9), (a23, b3, c2, d10), (a23,b3, c2, d11), (a23, b3, c2, d12), (a23, b3, c2, d13), (a23, b3, c2,d14), (a23, b3, c2, d15), (a23, b3, c2, d16), (a23, b3, c2, d17), (a23,b3, c2, d18), (a23, b3, c2, d19), (a23, b3, c2, d20), (a23, b3, c2,d21), (a23, b3, c2, d22), (a23, b3, c3, d1), (a23, b3, c3, d2), (a23,b3, c3, d3), (a23, b3, c3, d4), (a23, b3, c3, d5), (a23, b3, c3, d6),(a23, b3, c3, d17), (a23, b3, c3, d18), (a23, b3, c3, d9), (a23, b3, c3,d10), (a23, b3, c3, d11), (a23, b5, c3, d12) (a23, b3, c3, d13), (a23,b3, c3, d14), (a23, b3, c3, d15), (a23, b3, c3, d16), (a23, b3, c3,d17), (a23, b3, c3, d18), (a23, b3, c3, d19), (a23, b3, c3, d20), (a23,b3, c3, d21), (a23, b3, c3, d22), (a23, b4, c1, d1), (a23, b4, c1, d2),(a23, b4, c1, d3), (a23, b4, c1, d4), (a23, b4, c1, d5), (a23, b4, c1,d6), (a23, b4, c1, d7), (a23, b4, c1, d8), (a23, b4, c1, d9), (a23, b4,c1, d10), (a23, b4, c1, d11), (a23, b4, c1, d12), (a23, b4, c1, d13),(a23, b4, c1, d14), (a23, b4, c1, d15), (a23, b4, c1, d16), (a23, b4,c1, d17), (a23, b4, c1, d18), (a23, b4, c1, d19), (a23, b4, c1, d20),(a23, b4, c1, d21), (a23, b4, c1, d22), (a23, b4, c2, d1), (a23, b4, c2,d2), (a23, b4, c2, d3), (a23, b4, c2, d4), (a23, b4, c2, d5), (a23, b4,c2, d6), (a23, b4, c2, d7), (a23, b4, c2, d8), (a23, b4, c2, d9), (a23,b4, c2, d10), (a23, b4, c2, d11), (a23, b4, c2, d12), (a23, b4, c2,d13), (a23, b4, c2, d14), (a23, b4, c2, d15), (a23, b4, c2, d10), (a23,b4, c2, d17), (a23, b4, c2, d18), (a23, b4, c2, d19), (a23, b4, c2,d20), (a23, b4, c2, d21), (a23, b4, c2, d22), (a23, b4, c3, dl), (a23,b4, c3, d2), (a23, b4, c3, d3), (a23, b4, c3, d4), (a23, b4, c3, d5),(a23, b4, c3, d6), (a23, b4, c3, d7), (a23, b4, c3, d8), (a23, b4, c3,d9), (a23, b4, c3, d10), (a23, b4, c3, d11), (a23, b4, c3, d12), (a23,b4, c3, d13), (a23, b4, c3, d14), (a23, b4, c3, d15), (a23, b4, c3,d16), (a23, b4, c3, d17), (a23, b4, c3, d18), (a23, b4, c3, d19), (a23,b4, c3, d20), (a23, b4, c3, d21), (a23, b4, c3, d22), (a23, b5, c1, d1),(a23, b5, c1, d2), (a23, b5, c1, d3), (a23, b5, c1, d4), (a23, b5, c1,d5), (a23, b5, c1, d6), (a23, b5, c1, d7), (a23, b5, c1, d8), (a23, b5,c1, d9), (a23, b5, c1, d10), (a23, b5, c1, d11), (a23, b5, c1, d12),(a23, b5, c1, d13), (a23, b5, c1, d14), (a23, b5, c1, d15), (a23, b5,c1, d16), (a23, b5, c1, d17), (a23, b5, c1, d18), (a23, b5, c1, d19),(a23, b5, c1, d20), (a23, b5, c1, d21), (a23, b5, c1, d22), (a23, b5,c2, d1), (a23, b5, c2, d12), (a23, b5, c2, d3), (a23, b5, c2, d4), (a23,b5, c2, c5), (a23, b5, c2, d6), (a23, b5, c2, d7), (a23, b5, c2, d8),(a23, b5, c2, d9), (a23, b5, c2, d10), (a23, b5, c2, d11), (a23, b5, c2,d12), (a23, b5, c2, d13), (a23, b5, c2, d14), (a23, b5, c2, d15), (a23,b5, c2, d16), (a23, b5, c2, d17), (a23, b5, c2, d18), (a23, b5, c2,d19), (a23, b5, c2, d20), (a23, b5, c2, d21), (a23, b5, c2, d22), (a23,b5, c2, d1), (a23, b5, c3, d2), (a23, b5, c3, d3), (a23, b5, c3, d4),(a23, b5, c3, d5), (a23, b5, c3, d6), (a23, b5, c3, d7), (a23, b5, c3,d8), (a23, b5, c3, d9), (a23, b5, c3, d10), (a23, b5, c3, d11), (a23,b5, c3, d12), (a23, b5, c3, d13), (a23, b5, c3, d14), (a23, b5, c3,d15), (a23, b5, c3, d16), (a23, b5, c3, d17), (a23, b5, c3, d18), (a23,b5, c3, d19), (a23, b5, c3, d20), (a23, b5, c3, d21), (a23, b5, c3,d22), (a23, b5, c1, d1), (a23, b6, c1, d2), (a23, b6, c1, d3), (a23, b6,c1, d4), (a23, b6, c1, d5), (a23, b6, c1, d6), (a23, b6, c1, d7), (a23,b6, c1, d8), (a23, b6, c1, d9), (a23, b6, c1, d10), (a23, b6, c1, d11),(a23, b6, c1, d12), (a23, b6, c1, d13), (a23, b6, c1, d14), (a23, b6,c1, d15), (a23, b6, c1, d16), (a23, b6, c1, d17), (a23, b6, c1, d18),(a23, b6, c1, d19), (a23, b6, c1, d20), (a23, b6, c1, d21), (a23, b6,c1, d22), (a23, b6, c2, d1), (a23, b6, c2, d2), (a23, b6, c2, d3), (a23,b6, c2, d4), (a23, b6, c2, d5), (a23, b6, c2, d6), (a23, b6, c2, d7),(a23, b6, c2, d8), (a23, b6, c2, d9), (a23, b6, c2, d10), (a23, b6, c2,d11), (a23, b6, c2, d12), (a23, b6, c2, d13), (a23, b6, c2, d14), (a23,b6, c2, d15), (a23, b6, c2, d16), (a23, b6, c2, d17), (a23, b6, c2,d18), (a23, b6, c2, d19), (a23, b6, c2, d20), (a23, b6, c2, d21), (a23,b6, c2, d22), (a23, b6, c3, d1), (a23, b6, c3, d2), (a23, b6, c3, d3),(a23, b6, c3, d4), (a23, b6, c3, d5), (a23, b6, c3, d6), (a23, b6, c3,d7), (a23, b6, c3, d8), (a23, b6, c3, d9), (a23, b6, c3, d10), (a23, b6,c3, d11), (a23, b6, c3, d12), (a23, b6, c3, d13), (a23, b6, c3, d14),(a23, b6, c3, d15), (a23, b6, c3, d16), (a23, b6, c3, d17), (a23, b6,c3, d18), (a23, b6, c3, d19), (a23, b6, c3, d20), (a23, b6, c3, d21),(a23, b6, c3, d22), (a24, b1, c1, d1), (a24, b1, c1, d2), (a24, b1, c1,d3), (a24, b1, c1, d4), (a24, b1, c1, d5), (a24, b1, c1, d6), (a24, b1,c1, d7), (a24, b1, c1, d8), (a24, b1, c1, d9), (a24, b1, c1, d10), (a24,b1, c1, d11), (a24, b1, c1, d12), (a24, b1, c1, d13), (a24, b1, c1,d14), (a24, b1, c1, d15), (a24, b1, c1, d16), (a24, b1, c1, d17), (a24,b1, c1, d18), (a24, b1, c1, d19), (a24, b1, c1, d20), (a24, b1, c1,d21), (a24, b1, c1, d22), (a24, b1, c2, d1), (a24, b1, c2, d2), (a24,b1, c2, d3), (a24, b1, c2, d4), (a24, b1, c2, d5), (a24, b1, c2, d6),(a24, b1, c2, d7), (a24, b1, c2, d8), (a24, b1, c2, d9), (a24, b1, c2,d10), (a24, b1, c2, d11), (a24, b1, c1, d12), (a24, b1, c1, d13), (a24,b1, c1, d14), (a24, b1, c1, d15), (a24, b1, c1, d16), (a24, b1, c1,d17), (a24, b1, c1, d18), (a24, b1, c1, d19), (a24, b1, c1, d20), (a24,b1, c1, d21), (a24, b1, c1, d22), (a24, b1, c2, d1), (a24, b1, c2, d2),(a24, b1, c2, d3), (a24, b1, c2, d4), (a24, b1, c2, d5), (a24, b1, c2,d6), (a24, b1, c2, d7), (a24, b1, c2, d8), (a24, b1, c2, d9), (a24, b1,c2, d10) (a24, b1, c2, d11), (a24, b1, c2, d12), (a24, b1, c2, d13),(a24, b1, c2, d14), (a24, b1, c2, d15), (a24, b1, c2, d16), (a24, b1,c2, d17), (a24, b1, c2, d18), (a24, b1, c2, d19), (a24, b1, c2, d20),(a24, b1, c2, d21), (a24, b1, c2, d22), (a24, b1, c3, d1), (a24, b1, c3,d2), (a24, b1, c3, d3), (a24, b1, c3, d4), (a24, b1, c3, d5), (a24, b1,c3, d6), (a24, b1, c3, d7), (a24, b1, c3, d8), (a24, b1, c3, d9), (a24,b1, c3, d10), (a24, b1, c3, d11), (a24, b1, c3, d12), (a24, b1, c3,d13), (a24, b1, c3, d14), (a24, b1, c3, d15), (a24, b1, c3, d16), (a24,b1, c3, d17), (a24, b1, c3, d18), (a24, b1, c3, d19), (a24, b1, c3,d20), (a24, b1, c3, d21), (a24, b1, c3, d22), (a24, b2, c1, d1), (a24,b2, c1, d2), (a24, b2, c1, d3), (a24, b2, c1, d4), (a24, b2, c1, d5),(a24, b2, c1, d6), (a24, b2, c1, d7), (a24, b2, c1, d8), (a24, b2, c1,d9), (a24, b2, c1, d10), (a24, b2, c1, d11), (a24, b2, c1, d12), (a24,b2, c1, d13), (a24, b2, c1, d14), (a24, b2, c1, d15), (a24, b2, c1,d16), (a24, b2, c1, d17), (a24, b2, c1, d18), (a24, b2, c1, d19), (a24,b2, c1, d20), (a24, b2, c1, d21), (a24, b2, c1, d22), (a24, b2, c2, d1),(a24, b2, c2, d2), (a24, b2, c2, d3), (a24, b2, c2, d4), (a24, b2, c2,d5), (a24, b2, c2, d6), (a24, b2, c2, d7), (a24, b2, c2, d8), (a24, b2,c2, d9), (a24, b2, c2, d10), (a24, b2, c2, d11), (a24, b2, c2, d12),(a24, b2, c2, d13), (a24, b2, c2, d14), (a24, b2, c2, d15), (a24, b2,c2, d16), (a24, b2, c2, d17), (a24, b2, c2, d18), (a24, b2, c2, d19),(a24, b2, c2, d20), (a24, b2, c2, d21), (a24, b2, c2, d22), (a24, b2,c3, d1), (a24, b2, c3, d2), (a24, b2, c3, d3), (a24, b2, c3, d4), (a24,b2, c3, d5), (a24, b2, c3, d6), (a24, b2, c3, d7), (a24, b2, c3, d8),(a24, b2, c3, d9), (a24, b2, c3, d10), (a24, b2, c3, d11), (a24, b2, c3,d12), (a24, b2, c3, d13), (a24, b2, c3, d14), (a24, b2, c3, d15), (a24,b2, c3, d16), (a24, b2, c3, d17), (a24, b2, c3, d18), (a24, b2, c3,d19), (a24, b2, c3, d20), (a24, b2, c3, d21), (a24, b2, c3, d22), (a24,b3, c1, d1), (a24, b3, c1, d2), (a24, b3, c1, d3), (a24, b3, c1, d4),(a24, b3, c1, d5), (a24, b3, c1, d6), (a24, b3, c1, d7), (a24, b3, c1,d8), (a24, b3, c1, d9), (a24, b3, c1, d10), (a24, b3, c1, d11), (a24,b3, c1, d12), (a24, b3, c1, d13), (a24, b3, c1, d14), (a24, b3, c1,d15), (a24, b3, c1, d16), (a24, b3, c1, d17), (a24, b3, c1, d18), (a24,b3, c1, d19), (a24, b3, c1, d20), (a24, b3, c1, d21), (a24, b3, c1,d22), (a24, b3, c2, d1), (a24, b3, c2, d2), (a24, b3, c2, d3), (a24, b3,c2, d4), (a24, b3, c2, d5), (a24, b3, c2, d6), (a24, b3, c2, d7), (a24,b3, c2, d8), (a24, b3, c2, d9), (a24, b3, c2, d10), (a24, b3, c2, d11),(a24, b3, c2, d12), (a24, b3, c2, d13), (a24, b3, c2, d14), (a24, b3,c2, d15), (a24, b3, c2, d16), (a24, b3, c2, d17), (a24, b3, c2, d18),(a24, b3, c2, d19), (a24, b3, c2, d20), (a24, b3, c2, d21), (a24, b3,c2, d22), (a24, b3, c3, d1), (a24, b3, c3, d2), (a24, b5, c3, d3), (a24,b5, c3, d4), (a24, b3, c3, c3, d5), (a24, b3, c3, d6), (a24, b3, c3,d7), (a24, b3, c3, d8), (a24, b3, c3, d9), (a24, b3, c3, d10), (a24, b3,c3, d11), (a24, b3, b3, c3, d12), (a24, b3, c3, d13), (a24, b3, c3,d14), (a24, b3, c3, d15), (a24, b3, c3, d16), (a24, b3, c3, d17), (a24,b3, c3, d18), (a24, b3, c3, d19), (a24, b3, c3, d20), (a24, b3, c3,d21), (a24, b3, c3, d22), (a24, b4, c1, d1), (a24, b4, c1, d2), (a24,b4, c1, d3), (a24, b4, c1, d4), (a24, b4, c1, d5), (a24, b4, c1, d6),(a24, b4, c1, d7), (a24, b4, c1, d8), (a24, b4, c1, d9), (a24, b4, c1,d10), (a24, b4, c1, d11), (a24, b4, c1, d12), (a24, b4, c1, d13), (a24,b4, c1, d14), (a24, b4, c1, d15), (a24, b4, c1, d16), (a24, b4, c1,d17), (a24, b4, c1, d18), (a24, b4, c1, d19), (a24, b4, c1, d20), (a24,b4, c1, d21), (a24, b4, c1, d22), (a24, b4, c2, d1), (a24, b4, c2, d2),(a24, b4, c2, d3), (a24, b4, c2, d4), (a24, b4, c2, d5), (a24, b4, c2,d6), (a24, b4, c2, d7), (a24, b4, c2, d8), (a24, b4, c2, d9), (a24, b4,c2, d10), (a24, b4, c2, d11), (a24, b4, c2, d12), (a24, b4, c2, d13),(a24, b4, c2, d14), (a24, b4, c2, d15), (a24, b4, c2, d16), (a24, b4,c2, d7), (a24, b4, c2, d18), (a24, b4, c2, d19), (a24, b4, c2, d20),(a24, b4, c2, d21), (a24, b4, c2, d22), (a24, b4, c3, d1), (a24, b4, c3,d2), (a24, b4, c3, d3), (a24, b4, c3, d4), (a24, b4, c3, d5), (a24, b4,c3, d6), (a24, b4, c3, d7), (a24, b4, c3, d8), (a24, b4, c3, d9), (a24,b4, c3, d10), (a24, b4, c3, d11), (a24, b4, c3, d12), (a24, b4, c3,d13), (a24, b4, c3, d14), (a24, b4, c3, d15), (a24, b4, c3, d16), (a24,b4, c3, d17), (a24, b4, c3, d18), (a24, b4, c3, d19), (a24, b4, c3,d20), (a24, b4, c3, d21), (a24, b4, c3, d22), (a24, b5, c1, d1), (a24,b5, c1, d2), (a24, b5, c1, d3), (a24, b5, c1, d4), (a24, b5, c1, d5),(a24, b5, c1, d6), (a24, b5, c1, d7), (a24, b5, c1, d8), (a24, b5, c1,d9), (a24, b5, c1, d10), (a24, b5, c1, d11), (a24, b5, c1, d12), (a24,b5, c1, d13), (a24, b5, c1, d14), (a24, b5, c1, d15), (a24, b5, c1,d16), a24, b5, c1, d17), (a24, b5, c1, d18), (a24, b5, c1, d19), (a24,b5, c1, d20), (a24, b5, c1, d21), (a24, b5, c1, d22), (a24, b5, c2, d1),(a24, b5, c2, d2), (a24, b5, c2, d3), (a24, b5, c2, d4), (a24, b5, c2,d5), (a24, b5, c2, d6), (a24, b5, c2, d7), (a24, b5, c2, d8), (a24, b5,c2, d9), (a24, b5, c2, d10), (a24, b, c2, d11), (a24, b5, c2, d12),(a24, b5, c2, d13), (a24, b5, c2, d14), (a24, b5, c2, d15), (a24, b5,c2, d16), (a24, b5, c2, d17), (a24, b5, c2, d18), (a24, b5, c2, d19),(a24, b5, c2, d20), (a24, b5, c2, d21), (a24, b5, c2, d22), (a24, b5,c3, d1), (a24, b5, c3, d2), (a24, b5, c3, d5), (a24, b5, c3, d4), (a24,b5, c3, d5), (a24, b5, c3, d6), (a24, b5, c3, d7), (a24, b5, c3, d8),(a24, b, c3, d9), (a24, b5, c3, d10), (a24, b5, c3, d11), (a24, b5, c3,d12), (a24, b5, c3, d13), (a24, b5, c3, d14), (a24, b5, c3, d15), (a24,b5, c3, d16, (a24, b5, c3, d17), (a24, b5, c3, d18), (a24, b5, c3, d19),(a24, b5, c3, d20), (a24, b5, c3, d21), (a24, b5, c3, d22), (a24, b6,c1, d1), (a24, b6, c1, d2), (a24, b6, c1, d3), (a24, b6, c1, d4), (a24,b6, c1, d5), (a24, b6, c1, d6), (a24, b6, c1, d7), (a24, b6, c1, d8),(a24, b6, c1, d9), (a24, b6, c1, d10), (a24, b6, c1, d11), (a24, b6, c1,d12), (a24, b6, c1, d13), (a24, b5, c1, d14), (a24, b6, c1, d15), (a24,b6, c1, d16), (a24, b6, c1, d17), (a24, b6, c1, d18), (a24, b6, c1,d19), (a24, b6, c1, d20), (a24, b6, c1, d21), (a24, b6, c1, d22), (a24,b6, c2, d1), (a24, b6, c2, d2), (a24, b6, c2, d3), (a24, b6, c2, d4),(a24, b6, c2, d5), (a24, b6, c2, d6), (a24, b6, c2, d7), (a24, b6, c2,d8), (a24, b6, c2, d9), (a24, b6, c2, d6), (a24, b6, c2, d11), (a24, b6,c2, d12), (a24, b6, c2, d13), (a24, b6, c2, d14), (a24, b6, c2, d15),(a24, b6, c2, d16), (a24, b6, c2, d17), (a24, b6, c2, d18), (a24, b6,c2, d19), (a24, b6, c2, d20), (a24, b6, c2, d21), (a24, b6, c2, d22),(a24, b6, c3, d1), (a24, b6, c3, d2), (a24, b6, c3, d3), (a24, b6, c3,d4), (a24, b6, c3, d5), (a24, b6, c3, d6), (a24, b6, c3, d7), (a24, b6,c3, d8), (a24, b6, c3, d9), (a24, b6, c3, d10), (a24, b6, c3, d11),(a24, b6, c3, d12), (a24, b6, c3, d13), (a24, b6, c3, d14), (a24, b6,c3, d15), (a24, b6, c3, d16), (a24, b6, c3, d17), (a24, b6, c3, d18),(a24, b6, c3, d19), (a24, b6, c3, d20), (a24, b6, c3, d21), (a24, b6,c3, d22), (a25, b1, c1, d1), (a25, b1, c1, d2), (a25, b1, c1, d3), (a25,b1, c1, d4), (a25, b1, c1, d5), (a25, b1, c1, d6), (a25, b1, c1, d7),(a25, b1, c1, d8), (a25, b1, c1, d9), (a25, b1, c1, d10), (a25, b1, c1,d11), (a25, b1, c1, d12), (a25, b1, c1, d13), (a25, b1, c1, d14), (a25,b1, c1, d15), (a25, b1, c1, d16), (a25, b1, c1, d17), (a25, b1, c1,d18), (a25, b1, c1, d19), (a25, b1, c1, d20), (a25, b1, c1, d21), (a25,b1, c1, d22), (a25, b1, c2, d1), (a25, b1, c2, d2), (a25, b1, c2, d3),(a25, b1, c2, d4), (a25, b1, c2, d5), (a25, b1, c2, d6), (a25, b1, c2,d7), (a25, b1, c2, d8), (a25, b1, c2, d9), (a25, b1, c2, d10), (a25, b1,c2, d11), (a25, b1, c2, d12), (a25, b1, c2, d13), (a25, b1, c2, d14),(a25, b1, c2, d15), (a25, b1, c2, d16), (a25, b1, c2, d17), (a25, b1,c2, d18), (a25, b1, c2, d19), (a25, b1, c2, d20), (a25, b1, c2, d21),(a25, b1, c2, d22), (a25, b1, c3, d1), (a25, b1, c3, d2), (a25, b1, c3,d3), (a25, b1, c3, d4), (a25, b1, c3, d5), (a25, b1, c3, d6), (a25, b1,c3, d7), (a25, b1, c3, d8), (a25, b1, c3, d9), (a25, b1, c3, d10), (a25,b1, c3, d11), (a25, b1, c3, d12), (a25, b1, c3, d13), (a25, b1, c3,d14), (a25, b1, c3, d15), (a25, b1, c3, d16), (a25, b1, c3, d17), (a25,b1, c3, d18), (a25, b1, c3, d19), (a25, b1, c3, d20), (a25, b1, c3,d21), (a25, b1, c3, d22), (a25, b2, c1, d1), (a25, b2, c1, d2), (a25,b2, c1, d3), (a25, b2, c1, d4), (a25, b2, c1, d5), (a25, b2, c1, d6),(a25, b2, c1, d7), (a25, b2, c1, d8), (a25, b2, c1, d9), (a25, b2, c1,d10), (a25, b2, c1, d11), (a25, b2, c1, d12), (a25, b2, c1, d13), (a25,b2, c1, d14), (a25, b2, c1, d15), (a25, b2, c1, d16), (a25, b2, c1,d17), (a35, b2, c1, d18), (a25, b2, c1, d19), (a25, b2, c1, d20), (a25,b2, c1, d21), (a25, b2, c1, d22), (a25, b2, c2, d1), (a25, b2, c2, d2),(a25, b2, c2, d3), (a25, b2, c2, d4), (a25, b2, c2, d5), (a25, b2, c2,d6), (a25, b2, c2, d7), (a25, b2, c2, d8), (a25, b2, c2, d9), (a25, b2,c2, d10), (a25, b2, c2, d11), (a25, b2, c2, d12), (a25, b2, c2, d13),(a25, b2, c2, d14), (a25, b2, c2, d15), (a25, b2, c2, d16), (a25, b2,c2, d17), (a25, b2, c2, d18), (a25, b2, c2, d19), (a25, b2, c2, d20),(a25, b2, c2, d21), (a25, b2, c2, d22), (a25, b2, c3, d1), (a25, b2, c3,d2), (a25, b2, c3, d3), (a25, b2, c3, d4), (a25, b2, c3, d5), (a25, b2,c3, (d6), (a25, b2, c3, d7), (a25, b2, c3, d8), (a25, b2, c3, d9), (a25,b2, c3, d10), (a25, b2, c3, d11), (a25, b2, c3, d12), (a25, b2, c3,d13), (a25, b2, c3, d14), (a25, b2, c3, d15), (a25, b2, c3, d16), (a25,b2, c3, d17), (a25, b2, c3, d18), (a25, b2, c3, d19), (a25, b2, c3,d20), (a25, b2, c3, d21), (a25, b2, c3, d22), (a25, b3, c1, d1), (a25,b3, c1, d2), (a25, b3, c1, d3), (a25, b3, c1, d4), (a25, b3, c1, d5),(a25, b3, c1, d6), (a25, b3, c1, d7), (a25, b3, c1, d8), (a25, b3, c1,d9), (a25, b3, c1, d10), (a25, b3, c1, d11), (a25, b3, c1, d12), (a25,b3, c1, d13), (a25, b3, c1, d14), (a25, b3, c1, d15), (a25, b3, c1,d16), (a25, b3, c1, d17), (a25, b3, c1, d18), (a25, b3, c1, d19), (a25,b3, c1, d20), (a25, b3, c1, d21), (a25, b3, c1, d22), (a25, b3, c2, d1),(a25, b3, c2, d2), (a25, b3, c2, d3), (a25, b3, c2, d4), (a25, b3, c2,d5), (a25, b3, c2, d6), (a25, b3, c2, d7), (a25, b3, c2, d8), (a25, b3,c2, d9), (a25, b3, c2, d10), (a25, b3, c2, d11), (a25, b3, c2, d2),(a25, b3, c2, d13), (a25, b3, c2, d14), (a25, b3, c2, d15), (a25, b3,c2, d16), (a25, b3, c2, d17), (a25, b3, c2, d18), (a25, b3, c2, d19),(a25, b3, c2, d20), (a25, b3, c2, d21), (a25, b3, c2, d22), (a25, b3,c3, d1), (a25, b3, c3, d2), (a25, b3, c3, d3), (a25, b3, c3, d4), (a25,b3, c3, d5), (a25, b3, c3, d6), (a25, b3, c3, d7), (a25, b3, c3, d3),(a25, b3, c3, d9), (a25, b3, c3, d10), (a25, b3, c3, d11), (a25, b3, c3,d12), (a25, b3, c3, d13), (a25, b3, c3, d14), (a25, b3, c3, d15), (a25,b3, c3, d16), (a25, b3, c3, d17), (a25, b3, c3, d18), (a25, b3, c3,d19), (a25, b3, c3, d20), (a25, c3, c3, d21), (a25, b3, c3, d22), (a25,b4, c1, d1), (a25, b4, c1, d2), (a25, b4, c1, d3), (a25, b4, c1, d4),(a25, b4, c1, d5), (a25, b4, c1, d6), (a25, b4, c1, d7), (a25, b4, c1,d8), (a25, b4, c1, d9), (a25, b4, c1, d10), (a25, b4, c1, d11), (a25,b4, c1, d12), (a25, b4, c1, d13), (a25, b4, c1, d14), (a25, b4, c1,d15), (a25, b4, c1, d16), (a25, b4, c1, d17), (a25, b4, c1, d18), (a25,b4, c1, d19), (a25, b4, c1, d20), (a25, b4, c1, d21), (a25, b4, c1,d22), (a25, b4, c2, d1), (a25, b4, c2, d2), (a25, b4, c2, d3), (a25, b4,c2, d4), (a25, b4, c2, d5), (a25, b4, c2, d6), (a25, b4, c2, d7), (a25,b4, c2, d8), (a25, b4, c2, d9), (a25, b4, c2, d10), (a25, b4, c2, d11),(a25, b4, c2, d12), (a25, b4, c2, d13), (a25, b4, c2, d14), (a25, b4,c2, d15), (a25, b4, c2, d16), (a25, b4, c2, d17), (a25, b4, c2, d18),(a25, b4, c2, d19), (a25, b4, c2, d20), (a25, b4, c2, d21), (a25, b4,c2, d22), (a25, b4, c3, d1), (a25, b4, c3, d2), (a25, b4, c3, d3), (a25,b4, c3, d4), (a25, b4, c3, d5), (a25, b4, c3, d6), (a25, b4, c3, d7),(a25, b4, c3, d8), (a25, b4, c3, d9), (a25, b4, c3, d10), (a25, b4, c3,d11), (a25, b4, c3, d12), (a25, b4, c3, d13), (a25, b4, c3, d14), (a25,b4, c3, d15), (a25, b4, c3, d16), (a25, b4, c3, d17), (a25, b4, c3,d18), (a25, b4, c3, d19), (a25, b4, c3, d20), (a25, b4, c3, d21), (a25,b4, c3, d22), (a25, b5, c1, d1), (a25, b5, c1, d2), (a25, b5, c1, d3),(a25, b5, c1, d4), (a25, b5, c1, d5), (a25, b5, c1, d6), (a25, b5, c1,d7), (a25, c1, d8), (a25, b5, c1, d9), (a25, b5, c1, d10), (a25, b5, c1,d11), (a25, b5, c1, d12), (a25, b5, c1, d13), (a25, b5, c1, d14), (a25,b5, c1, d15), (a25, b5, c1, d16), (a25, b5, c1, d17), (a25, b5, c1,d18), (a25, b5, c1, d19), (a25, b5, c1, d20), (a25, b5, c1, d21), (a25,b5, c1, d22), (a25, b5, c2, d1), (a25, b5, c2, d2), (a25, b5, c2, d3),(a25, b5, c2, d4), (a25, b5, c2, d5), (a25, b5, c2, d6), (a25, b5, c2,d7), (a25, b5, c2, d8), (a25, b5, c2, d9), (a25, b5, c2, d10), (a25, b5,c2, d11), (a25, b5, c2, d12), (a25, b5, c2, d13), (a25, b5, c2, d14),(a25, b5, c2, d15), (a25, b5, c2, d16), (a25, b5, c2, d17), (a25, b5,c2, d18), (a25, b5, c2, d19), (a25, b5, c2, d20), (a25, b5, c2, d21),(a25, b5, c2, d22), (a25, b5, c3, d1), (a25, b5, c3, d2), (a25, b5, c3,d3), (a25, b5, c3, d4), (a25, b5, c3, d5), (a25, b5, c3, d6), (a25, b5,c3, d7), (a25, b5, c3, d8), (a25, b5, c3, d9), (a25, b5, c3, d10), (a25,b5, c3, d11), (a25, b5, c3, d12), (a25, b5, c3, d13), (a25, b5, c3,d14), (a25, b5, c3, d15), (a25, b5, c3, d16), (a25, b5, c3, d17), (a25,b5, c3, d18), (a25, b5, c3, d19), (a25, b5, c3, d20), (a25, b5, c3,d21), (a25, b5, c3, d22), (a25, b6, c1, d1), (a25, b6, c1, d2), (a25,b6, c1, d3), (a25, b6, c1, d4), (a25, b6, c1, d5), (a25, b6, c1, d6),(a25, b6, c1, d7), (a25, b6, c1, d8), (a25, b6, c1, d9), (a25, b6, c1,d10), (a25, b6, c1, d11), (a25, b6, c1, d12), (a25, b6, c1, d13), (a25,b6, c1, d14), (a25, b6, c1, d15), (a25, b6, c1, d16), (a25, b6, c1,d17), (a25, b6, c1, d18), (a25, b6, c1, d19), (a25, b6, c1, d20), (a25,b6, c1, d21), (a25, b6, c1, d22), (a25, b6, c2, d1), (a25, b6, c2, d2),(a25, b6, c2, d3), (a25, b6, c2, d4), (a25, b6, c2, d5), (a25, b6, c2,d6), (a25, b6, c2, d7), (a25, b6, c2, d8), (a25, b6, c2, d9), (a25, b6,c2, d10), (a25, b6, c2, d11), (a25, b6, c2, d12), (a25, b6, c2, d13),(a25, b6, c2, d14), (a25, b6, c2, d15), (a25, b6, c2, d16), (a25, b6,c2, d17), (a25, b6, c2, d18), (a25, b6, c2, d19), (a25, b6, c2, d20),(a25, b6, c2, d21), (a25, b6, c2, d22), (a25, b6, c3, d1), (a25, b6, c3,d2), (a25, b6, c3, d3), (a25, b6, c3, d4), (a25, b6, c3, d5), (a25, b6,c3, d6), (a25, b6, c3, d7), (a25, b6, c3, d8), (a25, b6, c3, d9), (a25,b6, c3, d10), (a25, b6, c3, d11), (a25, b6, c3, d12), (a25, b6, c3,d13), (a25, b6, c3, d14), (a25, b6, c3, d15), (a25, b6, c3, d16), (a25,b6, c3, d17), (a25, b6, c3, d18), (a25, b6, c3, d19), (a25, b6, c3,d20), (a25, b6, c3, d21), (a25, b6, c3, d22), (a26, b1, c1, d1), (a26,b1, c1, d2), (a26, b1, c1, d3), (a26, b1, c1, d4), (a26, b1, c1, d5),(a26, b1, c1, d6), (a26, b1, c1, d7), (a26, b1, c1, d8), (a26, b1, c1,d9), (a26, b1, c1, d10), (a26, b1, c1, d11), (a26, b1, c1, d12), (a26,b1, c1, d13), (a26, b1, c1, d14), (a26, b1, c1, d15), (a26, b1, c1,d16), (a26, b1, c1, d17), (a26, b1, c1, d18), (a26, b1, c1, d19), (a26,b1, c1, d20), (a26, b1, c1, d21), (a26, b1, c1, d22), (a26, b1, c2, d1),(a26, b1, c2, d2), (a26, b1, c2, d3), (a26, b1, c2, d4), (a26, b1, c2,d5), (a25, b1, c2, d6), (a26, b1, c2, d7), (a26, b1, c2, d8), (a26, b1,c2, d9), (a26, b1, c2, d10), (a26, b1, c2, d11), (a26, b1, c2, d12),(a26, b1, c2, d13), (a26, b1, c2, d14), (a26, b1, c2, d15), (a26, b1,c2, d16), (a26, b1, c2, d17), (a26, b1, c2, d18), (a26, b1, c2, d19),(a26, b1, c2, d20), (a26, b1, c2, d21), (a26, b1, c2, d22), (a26, b1,c2, d11), (a26, b1, c3, d2), (a26, b1, c3, d3), (a26, b1, c3, d4), (a26,b1, c3, d5), (a26, b1, c3, d6), (a26, b1, c3, d7), (a26, b1, c3, d8),(a26, b1, c3, d9), (a26, b1, c3, d16), (a26, b1, c3, d11), (a26, b1, c3,d12), (a26, b1, c3, d13), (a26, b1, c3, d14), (a26, b1, c3, d15), (a26,b1, c3, d16), (a26, b1, c3, d17), (a26, b1, c3, d18), (a26, b1, c3,d19), (a26, b1, c3, d20), (a26, b1, c3, d21), (a26, b1, c3, d22), (a26,b2, c1, d1), (a26, b2, c1, d2), (a26, b2, c1, d3), (a26, b2, c1, d4),(a26, b2, c1, d5), (a26, b2, c1, d6), (a26, b2, c1, d7), (a26, b2, c1,d8), (a26, b2, c1, d9), (a26, b2, c1, d10), (a26, b2, c1, d11), (a26,b2, c1, d12), (a26, b2, c1, d13), (a26, b2, c1, d14), (a26, b2, c1,d15), (a26, b2, c1, d16), (a26, b2, c1, d17), (a26, b2, c1, d18), (a26,b2, c1, d19), (a26, b2, c1, d20), (a26, b2, c1, d21), (a26, b2, c1,d22), (a26, b2, c2, d1), (a26, b2, c2, d2), (a26, b2, c2, d3), (a26, b2,c2, d4), (a26, b2, c2, d5), (a26, b2, c2, d6), (a26, b2, c2, d7), (a26,b2, c2, d8), (a26, b2, c2, d9), (a26, b2, c2, d10), (a26, b2, c2, d11),(a26, b2, c2, d12), (a26, b2, c2, d13), (a26, b2, c2, d14), (a6, b2, c2,d15), (a26, b2, c2, d16), (a26, b2, c2, d17), (a26, b2, c2, d18), (a26,b2, c2, d19), (a26, b2, c2, d20), (a26, b2, c2, d21), (a26, b2, c2,d22), (a26, b2, c3, d1), (a26, b2, c3, d2), (a26, b2, c3, d3, (a26, b2,c3, d4), (a26, b2, c3, d5), (a26, b2, c3, d6), (a26, b2, c3, d7), (a26,b2, c3, d8), (a26, b2, c3, d9), (a26, b2, c3, d10), (a26, b2, c3, d11),(a26, b2, c3, d12), (a26, b2, c3, d13), (a26, b2, c3, d14), (a26, b2,c3, d15), (a26, b2, c3, d16), (a26, b2, c3, d17), (a26, b2, c3, d18),(a26, b2, c3, d19), (a26, b2, c3, d20), (a26, b2, c3, d21), (a26, b2,c3, d22), (a26, b3, c1, d1), (a26, b3, c1, d2), (a26, b3, c1, d3), (a26,b3, c1, d4), (a36, b3, c1, d5), (a26, b3, c1, d6), (a26, b3, c1, d7),(a26, b3, c1, d18), (a26, b3, c1, d9), (a26, b3, c1, d10), (a26, b3, c1,d11), (a26, b3, c1, d12), (a26, b5, c1, d13), (a26, b3, c1, d14), (a26,b3, c1, d15), (a26, b3, c1, d16), (a26, b3, c1, d17), (a26, b3, c1,d18), (a26, b3, c1, d19), (a26, b3, c1, d20), (a26, b3, c1, d21), (a26,b3, c1, d22), (a26, b3, c2, d1), (a26, b3, c2, d2), (a26, b3, c2, d3),(a26, b3, c2, d4), (a26, b3, c2, d5), (a26, b3, c2, d6), (a26, b3, c2,d7), (a26, b3, c2, d3), (a26, b3, c2, d9), (a26, b3, c2, d10), (a26, b3,c2, d11), (a26, b3, c2, d12), (a26, b3, c2, d13), (a26, b3, c2, d14),(a26, b3, (a26, d15), (a26, b3, c2, d16), (a26, b3, c2, d17), (a26, b3,c2, d18), (a26, b3, c2, d19), (a26, b3, c2, d20), (a26, b3, c2, d21),(a26, b3, c2, d22), (a26, b3, c3, d1), (a26, b3, c3, d2), (a26, b3, c3,d3), (a26, b3, c3, d14), (a26, b3, c3, d5), (a26, b3, c3, d6), (a26, b3,c3, d7), (a26, b3, c3, d8), (a26, b3, c3, d9), (a26, b3, c3, d6), (a26,b3, c3, d11), (a26, b3, c3, d12), (a26, b3, c3, d13), (a26, b3, c3,d14), (a26, b3, c3, d15), (a26, b3, c3, d16), (a26, b3, c3, d17), (a26,b3, c3, d18), (a66, b3, c3, d19), (a26, b3, c3, d20), (a26, b3, c3,d21), (a26, b3, c3, d22), (a26, b4, c1, d1), (a26, b4, c1, d2), (a26,b4, c1, d3), (a26, b4, c1, d4), (a26, b4, c1, d5), (a26, b4, c1, d6),(a26, b4, c1, d7), (a26, b4, c1, d5), (a26, b4, c1, d9), (a66, b4, c1,d10), (a26, b4, c1, d11), (a26, b4, c1, d12), (a26, b4, c1, d13), (a26,b4, c1, d14), (a26, b4, c1, d15), (a26, b4, c1, d16), (a26, b4, c1,d17), (a26, b4, c1, d18), (a26, b4, c1, d19), (a26, b4, c1, d20), (a26,b4, c1, d21), (a26, b4, c1, d22), (a26, b4, c2, d1), (a6, b4, c2, d2),(a26, b4, c2, d3), (a26, b4, c2, d4), (a76, b4, c2, d5), (a26, b4, c2,d6), (a26, b4, c2, d7), (a76, b4, c2, d8), (a6, b4, c2, d9), (a26, b4,c2, d10), (a26, b4, c2, d11), (a66, b4, c2, d12), (a26, b4, c2, d13),(a26, b4, c2, d14), (a26, b4, c2, d15), (a26, b4, c2, d16), (a26, b4,c2, d17), (a26, b4, c2, d18), (a26, b4, c2, d19), (a26, b4, c2, d20),(a26, b4, c2, d21), (a26, b4, c2, d22), (a26, b4, c3, d1), (a26, b4, c3,d2), (a26, b4, c3, d3), (a26, b4, c3, d4), (a26, b4, c3, d5), (a26, b4,c3, d6), (a26, b4, c3, d7), (a26, b4, c3, d8), (a26, b4, c3, d9), (a26,b4, c3, d10), (a26, b4, c3, d11), (a26, b4, c3, d12), (a26, b4, c3,d13), (a26, b4, c3, d14), (a26, b4, c3, d15), (a26, b4, c3, d16), (a26,b4, c3, d17), (a26, b4, c3, d18), (a26, b4, c3, d19), (a26, b4, c3,d20), (a26, b4, c3, d21), (a26, b4, c3, d22), (a26, b5, c1, d1), (a26,b5, c1, d2), (a26, b5, c1, d3), (a26, b5, c1, d4), (a26, b5, c1, d5),(a26, b5, c1, d6), (a26, b5, c1, d7), (a26, b5, c1, d8), (a26, b5, c1,d9), (a26, b5, c1, d10), (a26, b5, c1, d11), (a26, b5, c1, d12), (a26,b5, c1, d3), (a26, b5, c1, d14), (a26, b5, c1, d15), (a26, b5, c1, d16),(a26, b5, c1, d17) (a26, b5, c1, d18), (a26, b5, c1, d19), (a26, b5, c2,d20), (a26, b5, c2, d21), (a26, b5, c2, d22), (a26, b5, c2, d1), (a26,b5, c2, d2), (a26, b5, c2, d3), (a26, b5, c2, d4), (a26, b5, c2, d5),(a26, b5, c2, d6), (a26, b5, c2, d7), (a26, b5, c2, d8), (a26, b5, c2,d9), (a26, b5, c2, d10), (a26, b5, c2, d11), (a26, b5, c2, d12), (a26,b5, c2, d13), (a26, b5, c2, d14), (a26, b5, c2, d15), (a26, b5, c2,d16), (a26, b5, c2, d17), (a26, b5, c2, d18), (a26, b5, c2, d19), (a26,b5, c2, d20), (a26, b5, c2, d21), (a26, b5, c2 d22), (a26, b5, c3, d1),(a26, b5, c3, d2), (a26, b5, c3, d3), (a26, b5, c3, d4), (a26, b5, c3,d5), (a26, b5, c3, d6), (a26, b5, c3, d7), (a26, b5, c3, d8), (a26, b5,c3, d9), (a26, b5, c3, d10), (a26, 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(a28, b1, c3, d9), (a28, b1, c3,d10), (a28, b1, c3, d11), (a28, b1, c3, d12), (a28, b1, c3, d13), (a28,b1, c3, d14), (a28, b1, c3, d15), (a28, b1, c3, d16), (a28, b1, c3,d17), (a28, b1, c3, d18), (a28, b1, c3, d19), (a28, b1, c3, d20), (a28,b1, c3, d21), (a28, b1, c3, d22), (a28, b2, c1, d1), (a28, b2, c1, d2),(a28, b2, c1, d3), (a28, b2, c1, d4), (a28, b2, c1, d5), (a28, b2, c1,d6), (a28, b2, c1, d7), (a28, b2, c1, d8), (a28, b2, c1, d9), (a28, b2,c1, d10), (a28, b2, c1, d11), (a28, b2, c1, d12), (a28, b2, c1, d13),(a28, b2, c1, d14), (a28, b2, c1, d15), (a28, b2, c1, d16), (a28, b2,c1, d17), (a28, b2, c1, d18), (a28, b2, c1, d19), (a28, b2, c1, d20),(a28, b2, c1, d21), (a28, b2, c1, d22), (a28, b2, c2, d1), (a28, b2, c2,d2), (a28, b2, c2, d3), (a28, b2, c2, d4), (a28, b2, c2, d5), (a28, b2,c2, d6), (a28, b2, c2, d7), (a28, b2, c2, d8), (a28, b2, c2, d9), (a28,b2, c2, d10), (a28, b2, c2, d11), (a28, b2, c2, d12), (a28, b2, c2,d13), (a28, b2, c2, d14), (a28, b2, c2, d15), (a28, b2, c2, 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b3, c2, d2), (a28, b3, c2, d3), (a28, b3, c2, d4), (a28,b3, c2, d5), (a28, b3, c2, d6), (a28, b3, c2, d7), (a28, b3, c2, d8),(a28, b3, c2, d9), (a28, b3, c2, d10), (a28, b3, c2, d11), (a28, b3, c2,d12), (a28, b3, c2, d13), (a28, b3, c2, d14), (a28, b3, c2, d15), (a28,b3, c2, d16), (a28, b3, c2, d17), (a28, b3, c2, d18), (a28, b3, c2,d19), (a28, b3, c2, d20), (a28, b3, c2, d21), (a28, b3, c2, d22), (a28,b3, c3, d1), (a28, b3, c3, d2), (a28, b3, c3, d3), (a28, b3, c3, d4),(a28, b3, c3, d5), (a28, b3, c3, d6), (a28, b3, c3, d7), (a28, b3, c3,d8), (a28, b3, c3, d9), (a28, b3, c3, d10), (a28, b3, c3, d11), (a28,b3, c3, d12), (a28, b5, c3, d13), (a28, b3, c3, d14), (a28, b3, c3,d15), (a28, b3, c3, d16), (a28, b3, c3, d17), (a28, b3, c3, d18), (a28,b3, c3, d19), (a28, b3, c3, d20), (a28, b3, c3, d21), (a28, b3, c3,d22), (a28, b4, c1, d1), (a28, b4, c1, d2), (a28, b4, c1, d3), (a28, b4,c1, d4), (a28, b4, c1, d5), (a28, b4, c1, d6), (a28, b4, c1, d7), (a28,b4, c1, d8), (a28, b4, c1, d9), (a28, 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b1, c1, d19),(a19, b1, c1, d20), (a29, b1, c1, d21), (a29, b, c1, d22), (a29, b1, c2,d1), (a29, b1, c2, d2), (a29, b1, c2, d3), (a29, b1, c2, d4), (a29, b1,c2, d5), (a29, b1, c2, d6), (a29, b1, c2, d7), (a29, b1, c2, d8), (a29,b1, c2, d9), (a29, b1, c2, d10), (a29, b1, c2, d11), (a29, b1, c2, d12),(a29, b1, c2, d13), (a29, b1, c2, d14), (a29, b1, c2, d15), (a29, b1,c2, d16), (a29, b1, c2, d17), (a29, b1, c2, d18), (a29, b1, c2, d19),(a29, b1, c2, d20), (a29, b1, c2, d21), (a29, b1, c2, d22), (a29, b1,c3, d1), (a29, b1, c3, d2), (a29, b1, c3, d3), (a29, b1, c3, d4), (a29,b1, c3, d5), (a29, b1, c3, d6), (a29, b1, c3, d7), (a29, b1, c3, d8),(a29, b1, c3, d9), (a29, b1, c3, d10), (a29, b1, c3, d11), (a29, b1, c3,d12), (a29, b1, c3, d13), (a29, b1, c3, d14), (a29, b1, c3, d15), (a29,b1, c3, d16), (a29, b1, c3, d17), (a29, b1, c3, d18), (a29, b1, c3,d19), (a29, b1, c3, d20), (a29, b1, c3, d21), (a29, b1, c3, d22), (a29,b2, c1, d1), (a29, b2, c1, d2), (a29, b2, c1, d3), (a29, b2, c1, d4),(a29, b2, c1, d5), (a29, b2, c1, d6), (a29, b2, c1, d7), (a29, b2, c1,d8), (a29, b2, c1, d9), (a29, b2, c1, d10), (a29, b2, c1, d11), (a29,b2, c1, d12), (a29, b2, c1, d13), (a29, b2, c1, d14), (a29, b2, c1,d15), (a29, b2, c1, d16), (a29, b2, c1, d17), (a29, b2, c1, d18), (a29,b2, c1, d19), (a29, b2, c1, d20), (a29, b2, c1, d21), (a29, b2, c1,d22), (a29, b2, c2, d1), (a29, b2, c2, d2), (a29, b2, c2, d3), (a29, b2,c2, d4), (a29, b2, c2, d5), (a29, b2, c2, d6), (a29, b2, c2, d7), (a29,b2, c2, d8), (a29, b2, c2, d9), (a29, b2, c2, d10), (a29, b2, c2, d11),(a29, b2, c2, d12), (a29, b2, c2, d13), (a29, b2, c2, d14), (a29, b2,c2, d15), (a29, b2, c2, d16), (a29, b2, c2, d17), (a29, b2, c2, d18),(a29, b2, c2, d19), (a29, b2, c2, d20), (a29, b2, (c2, d21), (a29, b2,c2, d22), (a29, b2, c3, d1), (a29, b2, c3, d2), (a29, b2, c3, d3), (a29,b2, c3, d4), (a29, b2, c3, d5), (a29, b2, c3, d6), (a29, b2, c3, d7),(a29, b2, c3, d8), (a29, b2, c3, d9), (a29, b2, c3, d10), (a29, b2, c3,d11), (a29, b2, c3, d12), (a29, b2, c3, d13), (a29, b2, c3, d14), (a29,b2, c3, d15), (a29, b2, c3, d16), (a29, b2, c3, d17), (a29, b2, c3,d18), (a29, b2, c3, d19), (a29, b2, c3, d20), (a29, b2, c3, d21), (a29,b2, c3, d22), (a29, b3, c1, d1), (a29, b3, c1, d2), (a29, b3, c1, d3),(a29, b3, c1, d4), (a29, b3, c1, d5), (a29, b3, c1, d6), (a29, b3, c1,d7), (a29, b3, c1, d8), (a29, b3, c1, d9), (a29, b3, c1, d10), (a29, b3,c1, d11), (a29, b3, c1, d12), (a29, b3, c1, d13), (a29, b3, c1, d14),(a29, b3, c1, d15), (a29, b3, c1, d16), (a29, b3, c1, d17), (a29, b3,c1, d18), (a29, b3, c1, d19), (a29, b3, c1, d20), (a29, b3, c1, d21),(a29, b3, c1, d22), (a29, b3, c2, d1), (a29, b3, c2, d2), (a29, b3, c2,d3), (a29, b3, c2, d4), (a29, b3, c2, d5), (a29, b3, c2, d6), (a29, b3,c2, d7), (a29, b3, c2, d6), (a29, b3, c2, d9), (a29, b3, c2, d10), (a29,b3, c2, d11), (a29, b3, c2, d12), (a29, b3, c2, d13), (a29, b3, c2,d14), (a29, b3, c2, d15), (a29, b3, c2, d16), (a29, b3, c2, d17), (a29,b3, c2, d18), (a29, b3, c2, d19), 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d5), (a29, b4,c2, d6), (a29, b4, c2, d7), (a29, b4, c2, d8), (a29, b4, c2, d9), (a29,b4, c2, d10), (a29, b4, c2, d11), (a29, b4, c2, d12), (a29, b4, c2,d13), (a29, b4, c2, d14), (a29, b4, c2, d15), (a29, b4, c2, d16), (a29,b4, c2, d17), (a29, b4, c2, d18), (a29, b4, c2, d19), (a29, b4, c2,d20), (a29, b4, c2, d21), (a29, b4, c2, d22), (a29, b4, c3, d1), (a29,b4, c3, d2), (a29, b4, c3, d3), (a29, b4, c3, d4), (a29, b4, c3, d5),(a29, b4, c3, d6), (a29, b4, c3, d7), (a29, b4, c3, d8), (a29, b4, c3,d9), (a29, b4, c3, d10), (a29, b4, c3, d11), (a29, b4, c3, d12), (a29,b4, c3, d13), (a29, b4, c3, d14), (a29, b4, c3, d15), (a29, b4, c3,d16), (a29, b4, c3, d17), (a29, b4, c3, d18), (a29, b4, c3, d19), (a29,b4, c3, d20), (a29, b4, c3, d21), (a29, b4, c3, d22), (a29, b5, c1, d1),(a29, b5, c1, d2), (a29, b5, c1, d3), (a29, b5, c1, d4), (a29, b5, c1,d5), (a29, b, c1, d6), (a29, b5, c1, d7), (a29, b5, c1, d8), (a29, b5,c1, d9), (a29, b5, c1, d10), (a29, b5, c1, d11), (a29, b5, c1, d12),(a29, b5, c1, 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c1, d8), (a30, b3,c1, d9), (a30, b3, c1, d10), (a30, b3, c1, d11), (a30, b3, c1, d12),(a30, b3, c1, d13), (a30, b3, c1, d14), (a30, b3, c1, d15), (a30, b3,c1, d16), (a30, b3, c1, d17), (a30, b3, c1, d18), (a30, b3, c1, d19),(a30, b3, c1, d20), (a30, b3, c1, d21), (a30, b3, c1, d22), (a30, b3,c2, d1), (a30, b3, c2, d2), (a30, b3, c2, d3), (a30, b3, c2, d4), (a30,b3, c2, d5), (a30, b3, c2, d6), (a30, b3, c2, d7), (a30, b3, c2, d8),(a30, b3, c2, d9), (a30, b3, c2, d10), (a30, b3, c2, d11), (a30, b3, c2,d12), (a30, b3, c2, d13), (a30, b3, c2, d14), (a60, b3, c2, d15), (a30,b3, c2, d16), (a30, b3, c2, d17), (a30, b3, c2, d18), (a30, b3, c2,d19), (a30, b3, c2, d20), (a30, b3, c2, d21), (a30, b3, c2, d22), (a30,b3, c3, d1), (a30, b3, c3, d2), (a30, b3, c3, d3), (a30, b3, c3, d4),(a30, b3, c3, d5), (a30, b3, c3, d6), (a30, b3, c3, d7), (a30, b3, c3,d8), (a30, b3, c3, d9), (a30, b3, c3, d10), (a30, b3, c3, d11), (a30,b3, c3, d12), (a30, b3, c3, d13), (a30, b6, c2, d14), (a30, b3, c3,d15), (a30, 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c1, d2), (a42, b4, c1, d3), (a42, b4, c1, d4),(a42, b4, c1, d5), (a42, b4, c1, d6), (a42, b4, c1, d7), (a42, b4, c1,d3), (a42, b4, c1, d9), (a42, b4, c1, die), (a42, b4, c1, d11), (a42,b4, c1, d12), (a42, b4, c1, d13), (a42, b4, c1, d14), (a42, b4, c1,d15), (a42, b4, c1, d16), (a42, b4, c1, d17), (a42, b4, c1, d18), (a42,b4, c1, d19), (a42, b4, c1, d20), (a42, b4, c1, d21), (a42, b4, c1,d22), (a42, b4, c2, d1), (a42, b4, c2, d2), (a42, b4, c2, d3), (a42, b4,c2, d4), (a42, b4, c2, d5), (a42, b4, c2, d6), (a42, b4, c2, d7), (a42,b4, c2, d8), (a42, b4, c2, d9), (a42, b4, c2, d10), (a42, b4, c2, d11),(a42, b4, c2, d12), (a42, b4, c2, d13), (a42, b4, c2, d14), (a42, b4,c2, d15), (a42, b4, c2, d16), (a42, b4, c2, d17), (a42, b4, c2, d18),(a42, b4, c2, d19), (a42, b4, c2, d20), (a42, b4, c2, d21), (a42, b4,c2, d22), (a42, b4, c3, d1), (a42, b4, c3, d2), (a42, b4, c3, d3), (a42,b4, c3, d4), (a42, b4, c3, d5), (a42, b4, c3, d6), (a42, b4, c3, d7),(a42, b4, c3, d8), (a42, b4, c3, d9), (a42, b4, 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(a42,b5, c2, d18), (a42, b5, c2, d19), (a42, b5, c2, d20), (a42, b5, c2,d21), (a42, b5, c2, d22), (a42, b5, c3, d1), (a42, b5, c3, d2), (a42,b5, c3, d3), (a42, b5, c3, d4), (a42, b5, c3, d5), (a42, b5, c3, d6),(a42, b5, c3, d7), (a42, b5, c3, d8), (a42, b5, c3, d9), (a42, b5, c3,d10), (a42, b5, c3, d11), (a42, b5, c3, d12), (a42, b5, c3, d13), (a42,b5, c3, d14), (a42, b5, c3, d15), (a42, b5, c3, d16), (a42, b5, c3,d17), (a42, b5, c3, d18), (a42, b5, c3, d19), (a42, b5, c3, d20), (a42,b5, c3, d21), (a42, b5, c3, d22), (a42, b6, c1, d1), (a42, b6, c1, d2),(a42, b6, c1, d3), (a42, b6, c1, d4), (a42, b6, c1, d5), (a42, b6, c1,d6), (a42, b6, c1, d7), (a42, b6, c1, d8), (a42, b6, c1, d9), (a42, b6,c1, d10), (a42, b6, c1, d11), (a42, b6, c1, d12), (a42, b6, c1, d13),(a42, b6, c1, d14), (a42, b6, c1, d15), (a42, (a42, b6, c1, d16), (a42,b6, c1, d17), (a42, b6, c1, d18), (a42, b6, c1, d19), (a42, b6, c1,d20), (a42, b6, c1, d21), (a42, b6, c1, d22), (a42, b6, c2, d1), (a42,b6, c2, d2), (a42, b6, c2, d3), (a42, b6, c2, d4), (a42, b6, c2, d5),(a42, b6, c2, d6), (a42, b6, c2, d7), (a42, b6, c2, d8), (a42, b6, c2,d9), (a42, b6, c2, d10), (a42, b6, c2, d11), (a42, b6, c2, d12), (a42,b6, c2, d13), (a42, b6, c2, d14), (a42, b6, c2, d15), (a42, b6, c2,d16), (a42, b6, c2, d17), (a42, b6, c2, d18), (a42, b6, c1, d19), (a42,b6, c2, d20) (a42, b6, c2, d21), (a42, b6, c2, d22), (a42, b6, c3, d1),(a42, b6, c3, d2), (a42, b6, c3, d3), (a42, b6, c3, d3), (a42, b6, c3,d3), (a42, b6, c3, d3), (a42, b6, c3, d7), (a42, b6, c3, d8), (a42, b6,c3, d9), (a42, b6, c3, d10), (a42, b6, c3, d11), (a42, b6, c3, d12),(a42, b6, c3, d13), (a42, b6, c3, d14), (a42, b6, c3, d15), (a42, b6,c3, d16), (a42, b6, c3, d17), (a42, b6, c3, d18), (a42, b6, c3, d19),(a42, b6, c3, d20), (a42, b6, c3, d21), (a42, b6, c3, d22), (a43, b1,c1, d1), (a43, b1, c1, d2), (a43, b1, c1, d3), (a43, b1, c1, d4), (a43,b1, c1, d5), (a43, b1, c1, d6), (a43, b1, c1, d7), (a43, b1, c1, d8),(a43, b1, c1, d9), (a43, b1, c1, d10), (a43, b1, 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(a43, b2, c3, d5), (a43, b2, c3, d6), (a43, b2, c3,d7), (a43, b2, c3, d8), (a43, b2, c3, d9), (a43, b2, c3, d10), (a43, b2,c3, d11), (a43, b2, c3, d12), (a43, b2, c3, d13), (a43, b2, c3, d14),(a43, b2, c3, d15), (a43, b2, c3, d16), (a43, b2, c3, d17), (a43, b2,c3, d18), (a43, b2, c3, d19), (a43, b2, c3, d20), (a43, b2, c3, d21),(a43, b2, c3, d22), (a43, b3, c1, d1), (a43, b3, c1, d2), (a43, b3, c1,d3), (a43, b3, c1, d4), (a43, b3, c1, d5), (a43, b3, c1, d6), (a43, b3,c1, d7), (a43, b3, c1, d8), (a43, b3, c1, d9), (a43, b3, c1, d10), (a43,b3, c1, d11), (a43, b3, c1, d12), (a43, b3, c1, d13), (a43, b3, c1,d14), (a43, b3, c1, d15), (a43, b3, c1, d16), (a43, b3, c1, d17), (a43,b3, c1, d18), (a43, b3, c1, d19), (a43, b3, c1, d20), (a43, b3, c1,d21), (a43, b3, c1, d22), (a43, b3, c2, d1), (a43, b3, c2, d2), (a43,b3, c2, d3), (a43, b3, c2, d4), (a43, b3, c2, d5), (a43, b3, c2, d6),(a43, b3, c2, d7), (a43, b3, c2, d8), (a43, b3, c2, d9), (a43, b3, c2,d10), (a43, b3, c2, d11), (a43, b3, c2, 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b2, c2, d14), (a51, b2, c2, d15), (a51, b2, c2,d16), (a51, b2, c2, d17), (a51, b2, c2, d18), (a51, b2, c2, d19), (a51,b2, c2, d20), (a51, b2, c2, d21), (a51, b2, c2, d22), (a51, b2, c3, d1),(a51, b2, c3, d2), (a51, b2, c3, d3), (a51, b2, c3, d4), (a51, b2, c3,d5), (a51, b2, c3, d6), (a51, b2, c3, d7), (a51, b2, c3, d8), (a51, b2,c3, d9), (a51, b2, c3, d10), (a51, b2, c3, d11), (a51, b2, c3, d12),(a51, b2, c3, d13), (a51, b2, c3, d14), (a51, b2, c3, d15), (a51, b2,c3, d16), (a51, b2, c3, d17), (a51, b2, c3, d18), (a51, b2, c3, d19),(a51, b2, c3, d20), (a51, b2, c3, d21), (a51, b2, c3, d22), (a51, b3,c1, d1), (a51, b3, c1, d2), (a51, b3, c1, d3), (a51, b3, c1, d4), (a51,b3, c1, d5), (a51, b3, c1, d6), (a51, b3, c1, d7), (a51, b3, c1, d8),(a15, b3, c1, d9), (a51, b3, c1, d1), (a51, b3, c1, d11), (a51, b3, c1,d12), (a51, b3, c1, d13), (a51, b3, c1, d14), (a51, b3, c1, d15), (a51,b3, c1, d16), (a51, b3, c1, d17), (a51, b3, c1, d18), (a51, b3, c1,d19), (a51, b3, c1, d20), (a51, b3, c1, d21), 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(a52, b6, c3, d5), (a52, b6, c3, d6),(a52, b6, c3, d7), (a52, b6, c3, d8), (a52, b6, c3, d9), (a52, b6, c3,d10), (a52, b6, c3, d11), (a52, b6, c3, d12), (a52, b6, c3, d13), (a52,b6, c3, d14), (a52, b6, c3, d15), (a52, b6, c3, d16), (a52, b6, c3,d17), (a52, b6, c3, d18), (a52, b6, c3, d19), (a52, b6, c3, d20), (a52,b6, c3, d21), (a52, b6, c3, d22), (a53, b1, c1, d1), (a53, b1, c1, d2),(a53, b1, c1, d3), (a53, b1, c1, d4), (a53, b1, c1, d5), (a53, b1, c1,d6), (a53, b1, c1, d7), (a53, b1, c1, d8), (a53, b1, c1, d9), (a53, b1,c1, d10), (a53, b1, c1, d11), (a53, b1, c1, d12), (a53, b1, c1, d13),(a53, b1, c1, d14), (a53, b1, c1, d15), (a53, b1, c1, d16), (a53, b1,c1, d17), (a53, b1, c1, d18), (a53, b1, c1, d19), (a53, b1, c1, d20),(a53, b1, c1, d21), (a53, b1, c1, d22), (a53, b1, c2, d1), (a53, b1, c2,d2), (a53, b1, c2, d3), (a53, b1, c2, d4), (a53, b1, c2, d5), (a53, b1,c2, d6), (a53, b1, c2, d7), (a53, b1, c2, d8), (a53, b1, c2, d9), (a53,b1, c2, d10), (a53, b1, c2, d11), (a53, b1, c2, d12), (a53, b1, c2,d13), (a53, b1, c2, d14), (a53, b1, c2, d15), (a53, b1, c2, d16), (a53,b1, c2, d17), (a53, b1, c2, d18), (a53, b1, c2, d19), (a53, b1, c2,d20), (a53, b1, c2, d21), (a53, b1, c2, d22), (a53, b1, c3, d1), (a53,b1, c3, d2), (a5, b1, c3, d3), (a53, b1, c3, d4), (a53, b1, c3, d5),(a53, b1, c3, d6), (a53, b1, c3, d7), (a53, b1, c3, d8), (a53, b1, c3,d9), (a53, b1, c3, d10), (a53, b1, c3, d11), (a53, b1, c3, d12), (a53,b1, c3, d13), (a53, b, c3, d14), (a53, b1, c3, d15), (a53, b1, c3, d16),(a53, b1, c3, d17), (a53, b1, c3, d18), (a53, b1, c3, d19), (a53, b1,c3, d20), (a53, b1, c3, d21), (a53, b1, c3, d22), (a53, b2, c1, d1),(a53, b2, c1, d2), (a53, b2, c1, d3), (a53, b2, c1, d4), (a53, b2, c1,d5), (a53, b2, c1, d6), (a53, b2, c1, d7), (a53, b2, c1, d8), (a53, b2,c1, d9), (a53, b2, c1, d10), (a53, b2, c1, d11), (a53, b2, c1, d12),(a53, b2, c1, d13), (a53, b2, c1, d14), (a53, b2, c1, d15), (a53, b2,c1, d16), (a53, b2, c1, d17), (a53, b2, c1, d18), (a53, b2, c1, d19),(a53, b2, c1, d20), (a53, b2, c1, d21), (a53, b2, c1, d22), (a53, b2,c2, d1), (a53, b2, c2, d2), (a53, b2, c2, d3), (a53, b2, c2, d4), (a53,b2, c2, d5), (a53, b2, c2, d6), (a53, b2, c2, d7), (a53, b2, c2, d8),(a53, b2, c2, d9), (a53, b2, c2, d10), (a53, b2, c2, d11), (a53, b2, c2,d12), (a53, b2, c2, d13), (a53, b2, c2, d14), (a53, b2, c2, d15), (a53,b2, c2, d16), (a53, b2, c2, d17), (a53, b2, c2, d18), (a53, b2, c2,d19), (a53, b2, c2, d20), (a53, b2, c2, d21), (a53, b2, c2, d22), (a53,b2, c3, d1), (a53, b2, c3, d2), (a53, b2, c3, d3), (a53, b2, c3, d4),(a53, b2, c3, d5), (a53, b2, c3, d6), (a53, b2, c3, d7), (a53, b2, c3,d8), (a53, b2, c3, d9), (a53, b2, c3, d10), (a53, b2, c3, d11), (a53,b2, c3, d12), (a53, b2, c3, d13), (a53, b2, c3, d14), (a53, b2, c3,d15), (a53, b2, c3, d16), (a53, b2, c3, d17), (a53, b2, c3, d18), (a53,b2, c3, d19), (a53, b2, c3, d20), (a53, b2, c3, d21), (a53, b2, c3,d22), (a53, b3, c1, d1), (a53, b3, c1, d2), (a53, b3, c1, d3), (a53, b3,c1, d4), (a53, b3, c1, d5), (a53, b3, c1, d6), (a53, b3, c1, d7), (a53,b3, c1, d8), (a53, b3, c1, d9), (a53, b3, c1, d10), (a53, b3, c1, d11),(a53, b3, c1, d12), (a53, b5, c1, d13), (a53, b5, c1, d14), (a53, b5,c1, d15), (a53, b3, c1, d16), (a53, b3, c1, d17), (a53, b3, c1, d18),(a53, b3, c1, d19), (a53, b3, c1, d20), (a53, b3, c1, d21), (a53, b3,c1, d22), (a53, b3, c2, d1), (a53, b3, c2, d2), (a53, b3, c2, d3), (a53,b3, c2, d4), (a53, b3, c2, d5), (a53, b3, c2, d6), (a53, b3, c2, d7),(a53, b3, c2, d8), (a53, b3, c2, d9), (a53, b3, c2, d10), (a53, b3, c2,d11), (a53, b3, c2, d12), (a53, b3, c2, d13), (a53, b3, c2, d14), (a53,b5, c2, d15), (a53, b5, c2, d16), (a53, b5, c2, d17), (a53, b3, c2,d18), (a53, b3, c2, d19), (a53, b3, c2, d20), (a53, b3, c2, d21), (a53,b3, c2, d22), (a53, b3, c3, d1), (a53, b3, c3, d2), (a53, b3, c3, d3),(a53, b3, c3, d4), (a53, b3, c3, d5), (a53, b3, c3, d6), (a53, b3, c3,d7), (a53, b3, c3, d8), (a53, b3, c3, d9), (a53, b3, c3, d10), (a53, b3,c3, d11), (a53, b3, c3, d12), (a53, b3, c3, d14), (a53, b3, c3, d15),(a53, b3, c3, d16), (a53, b3, c3, d17), (a53, b3, c3, d18), (a53, b3,c3, d19), (a53, b3, c3, d20), (a53, b3, c3, d21), (a53, b3, c3, d22),(a53, b4, c1, d1), (a53, b4, c1, d2), (a53, b4, c1, d3), (a53, b4, c1,d4), (a53, b4, c1, d5), (a53, b4, c1, d6), (a53, b4, c1, d7), (a53, b4,c1, d8), (a53, b4, c1, d9), (a53, b4, c1, d10), (a53, b4, c1, d11),(a53, b4, c1, d12), (a53, b4, c1, d13), (a53, b4, c1, d14), (a53, b4,c1, d15), (a53, b4, c1, d16), (a53, b4, c1, d17), (a53, b4, c1, d18),(a53, b4, c1, d19), (a53, b4, c1, d20), (a53, b4, c1, d21), (a53, b4,c1, d22), (a53, b4, c2, d1), (a53, b4, c2, d2), (a53, b4, c2, d3), (a53,b4, c2, d4), (a53, b4, c2, d5), (a53, b4, c2, d6), (a53, b4, c2, d7),(a53, b4, c2, d8), (a53, b4, c2, d9), (a53, b4, c2, d10), (a53, b4, c2,d11), (a53, b4, c2, d12), (a53, b4, c2, d13), (a53, b4, c2, d14), (a53,b4, c2, d15), (a53, b4, c2, d16), (a53, b4, c2, d17), (a53, b4, c2,d18), (a53, b4, c2, d19), (a53, b4, c2, d20), (a53, b4, c2, d21), (a53,b4, c2, d22), (a53, b4, c3, d1), (a53, b4, c3, d2), (a53, b4, c3, d3),(a53, b4, c3, d4), (a53, b4, c3, d5), (a53, b4, c3, d6), (a53, b4, c3,d7), (a53, b4, c3, d8), (a53, b4, c3, d9), (a53, b4, c3, d10), (a53, b4,c3, d11), (a53, b4, c3, d12), (a53, b4, c3, d13), (a53, b4, c3, d14),(a3, b4, c3, d15), (a53, b4, c3, d16), (a53, b4, c3, d17), (a53, b4, c3,d18), (a53, b4, c3, d19), (a53, b4, c3, d20), (a53, b4, c3, d21), (a53,b4, c3, d22), (a53, b5, c1, d1), (a53, b5, c1, d2), (a53, b5, c1, d3),(a53, b5, c1, d4), (a53, b5, c1, d5), (a53, b, c1, d6), (a53, b5, c1,d7), (a53, b5, c1, d8), (a53, b5, c1, d9), (a53, b5, c1, d10), (a53, b5,c1, d11), (a53, b5, c1, d12), (a53, b5, c1, d13), (a53, b5, c1, d14),(a53, b5, c1, d15), (a53, b5, c1, d16), (a53, b5, c1, d17), (a53, b5,c1, d18), (a53, b5, c1, dig), (a53, b5, c1, d20), (a53, b5, c1, d21),(a53, b5, c1, d22), (a53, b5, c2, d1), (a53, b5, c2, d2), (a53, b5, c2,d3), (a53, b5, c2, d4), (a53, b5, c2, d5), (a53, b5, c2, d6), (a53, b5,c2, d7), (a53, b5, c2, d8), (a53, b5, c2, d9), (a53, b5, c2, d10), (a53,b5, c2, d11), (a53, b5, c2, d12), (a53, b5, c2, d13), (a53, b5, c2,d14), (a53, b5, c2, d15), (a53, b5, c2, d16), (a53, b5, c2, d17), (a53,b5, c2, d18), (a53, b5, c2, d19), (a53, b5, c2, d20), (a53, b5, c2,d21), (a53, b5, c2, d22), (a53, b5, c3, d1), (a53, b5, c3, d2), (a53,b5, c3, d3), (a53, b5, c3, d4), (a53, b5, c3, d5), (a53, b5, c3, d6),(a53, b5, c3, d7), (a53, b5, c3, d8), (a53, b5, c3, d9), (a53, b5, c3,d10), (a53, b5, c3, d11), (a53, b5, c3, d12), (a53, b5, c3, d13), (a53,b5, c3, d14), (a53, b5, c3, d15), (a53, b5, c3, d16), (a53, b5, c3,d17), (a53, b5, c3, d18), (a53, b5, c3, d19), (a53, b5, c3, d20), (a53,b5, c3, d21), (a53, b5, c3, d22), (a53, b6, c1, d1), (a53, b6, c1, d2),(a53, b6, c1, d3), (a53, b6, c1, d4), (a53, b6, c1, d5), (a53, b6, c1,d6), (a53, b6, c1, d7), (a53, b6, c1, d8), (a53, b6, c1, d9), (a53, b6,c1, d10), (a53, b6, c1, d11), (a53, b6, c1, d12), (a53, b6, c1, d13),(a53, b6, c1, d14), (a53, b6, c1, d15), (a53, b6, c1, d16), (a53, b6,c1, d17), (a53, b6, c1, d18), (a53, b6, c1, d19), (a53, b6, c1, d20),(a53, b6, c1, d21), (a53, b6, c1, d22), (a53, b6, c2, d1), (a53, b6, c2,d2), (a53, b6, c2, d3), (a53, b6, c2, d4), (a53, b6, c2, d5), (a53, b6,c2, d6), (a53, b6, c2, d7), (a53, b6, c2, d8), (a53, b6, c2, d9), (a53,b6, c2, d10), (a53, b6, c2, d11), (a53, b6, c2, d12), (a53, b6, c2,d13), (a53, b6, c2, d14), (a53, b6, c2, d15), (a53, b6, c2, d16), (a53,b6, c2, d17), (a53, b6, c2, d18), (a53, b6, c2, d19), (a53, b6, c2,d20), (a53, b6, c2, d21), (a53, b6, c2, d22), (a53, b6, c3, d1), (a53,b6, c3, d2), (a53, b6, c3, d3), (a53, b6, c3, d4), (a53, b6, c3, d5),(a53, b6, c3, d6), (a53, b6, c3, d7), (a53, b6, c3, d8), (a53, b6, c3,d9), (a53, b6, c3, d10), (a53, b6, c3, d11), (a53, b6, c3, d12), (a53,b6, c3, d13), (a53, b6, c3, d14), (a53, b6, c3, d15), (a53, b6, c3,d16), (a53, b6, c3, d17), (a53, b6, c3, d18), (a53, b6, c3, d19), (a53,b6, c3, d20), (a53, b6, c3, d21), (a53, b6, c3, d22), (a54, b1, c1, d1),(a54, b1, c1, d2), (a54, b1, c1, d3), (a54, b1, c1, d4), (a54, b1, c1,d5), (a54, b1, c1, d6), (a54, b1, c1, d7), (a54, b1, c1, d8), (a54, b1,c1, d9), (a54, b1, c1, d10), (a54, b1, c1, d11), (a54, b1, c1, d12),(a54, b1, c1, d13), (a54, b1, c1, d14), (a54, b1, c1, d15), (a54, b1,c1, d16), (a54, b1, c1, d17), (a54, b1, c1, d18), (a54, b1, c1, d19),(a54, b1, c1, d20), (a54, b1, c1, d21), (a54, b1, c1, d22), (a54, b1,c2, d1), (a54, b1, c2, d2), (a54, b1, c2, d3), (a54, b1, c2, d4), (a54,b1, c2, d5), (a54, b1, c2, d6), (a54, b1, c2, d7), (a54, b1, c2, d8),(a54, b1, c2, d9), (a54, b1, c2, d10), (a54, b1, c2, d11), (a54, b1, c2,d12), (a54, b1, c2, d13), (a54, b1, c2, d14), (a54, b1, c2, d15), (a54,b1, c2, d16), (a54, b1, c2, d17), (a54, b1, c2, d18), (a54, b1, c2,d19), (a54, b1, c2, d20), (a54, b1, c2, d21), (a54, b1, c2, d22), (a54,b1, c3, d1), (a54, b1, c3, d2), (a54, b1, c3, d3), (a54, b1, c3, d4),(a54, b1, c3, d5), (a54, b1, c3, d6), (a54, b1, c3, d7), (a54, b1, c3,d8), (a54, b1, c3, d9), (a54, b1, c3, d10), (a54, b1, c3, d11), (a54,b1, c3, d12), (a54, b1, c3, d13), (a54, b1, c3, d14), (a54, b1, c3,d15), (a54, b1, c3, d16), (a54, b1, c3, d17), (a54, b1, c3, d18), (a54,b1, c3, d19), (a54, b1, c3, d20), (a54, b1, c3, d21), (a54, b1, c3,d22), (a54, b2, c1, d1), (a54, b2, c1, d2), (a54, b2, c1, d3), (a54, b2,c1, d4), (a54, b2, c1, d5), (a54, b2, c1, d6), (a54, b2, c1, d7), (a54,b2, c1, d8), (a54, b2, c1, d9), (a54), b2, c1, d10), (a54, b2, c1, d11),(a54, b2, c1, d12), (a54, b2, c1, d13), (a54, b2, c1, d14), (a54, b2,c1, d15), (a54, b2, c1, d16), (a54, b2, c1, d17), (a54, b2, c1, d18),(a54, b2, c1, d19), (a54, b2, c1, d20), (a54, b2, c1, d21), (a54, b2,c1, d22), (a54, b2, c2, d1), (a54, b2, c2, d2), (a54, b2, c2, d3), (a54,b2, c2, d4), (a54, b2, c2, d5), (a54, b2, c2, d6), (a54, b2, c2, d7),(a54, b2, c2, d8), (a54, b2, c2, d9), (a54, b2, c2, d10), (a54, b2, c2,d11), (a54, b2, c2, d12), (a54, b2, c2, d13), (a54, b2, c2, d14), (a54,b2, c2, d15), (a54, b2, c2, d16), (a54, b2, c2, d17), (a54, b2, c2,d18), (a54, b2, c2, d19), (a54, b2, c2, d20), (a54, b2, c2, d21), (a54,b2, c2, d22), (a54, b2, c3, d1), (a54, b2, c3, d2), (a54, b2, c3, d3),(a54, b2, c3, d4), (a54, b2, c3, d5), (a54, b2, c3, d6), (a54, b2, c3,d7), (a54, b2, c3, d8), (a54, b2, c3, d9), (a54, b2, c3, d10), (a54, b2,c3, d11), (a54, b2, c3, d12), (a54, b2, c3, d13), (a54, b2, c3, d14),(a54, b2, c3, d15), (a54, b2, c3, d16), (a54, b2, c3, d17), (a54, b2,c3, d18), (a54, b2, c3, d19), (a54, b2, c3, d20), (a54, b2, c3, d21),(a54, b2, c3, d22), (a54, b3, c1, d1), (a54, b3, c1, d2), (a54, b3, c1,d3), (a54, b3, c1, d4), (a54, b3, c1, d5), (a54, b3, c1, d6), (a54, b3,c1, d7), (a54, b3, c1, d8), (a54, b3, c1, d9), (a54, b3, c1, d10), (a54,b3, c1, d11), (a54, b3, c1, d12), (a54, b3, c1, d13), (a54, b3, c1,d14), (a54, b3, c1, d15), (a54, b3, c1, d16), (a54, b3, c1, d17), (a54,b3, c1, d13), (a54, b3, c1, d19), (a54, b3, c1, d20), (a54, b3, c1,d21), (a54, b3, c1, d22), (a54, b3, c2, d1), (a54, b3, c2, d2), (a54,b3, c2, d3), (a54, b3, c2, d4), (a54, b3, c2, d5), (a54, b3, c2, d6),(a54, b3, c2, d7), (a54, b3, c2, d8), (a54, b3, c2, d9), (a54, b3, c2,d10), (a54, b3, c2, d11), (a54, b3, c2, d2), (a54, b3, c2, d3), (a54,b3, c2, d14), (a54, b3, c2, d15), (a54, b3, c2, d16), (a54, b3, c2,d17), (a54, b3, c2, d18), (a54, b3, c2, d19), (a54, b3, c2, d20), (a54,b3, c2, d21), (a54, b3, c2, d22), (a54, b3, c3, d1), (a54, b3, c3, d2),(a54, b3, c3, d3), (a54, b3, c3, d4), (a54, b3, c3, d5), (a54, b3, c3,d6), (a54, b3, c3, d7), (a54, b3, c3, d8), (a54, b3, c3, d9), (a54, b3,c3, d10), (a54, b3, c3, d11), (a54, b3, c3, d2), (a54, b5, c3, d13),(a54, b3, c3, d14), (a54, b3, c3, d15), (a54, b3, c3, d16), (a54, b3,c3, d17), (a54, b3, c3, d18), (a54, b3, c3, d19), (a54, b3, c3, d20),(a54, b3, c3, d21), (a54, b3, c3, d22), (a54, b4, c1, d1), (a54, b4, c1,d2), (a54, b4, c1, d3), (a54, b4, c1, d4), (a54, b4, c1, d5), (a54, b4,c1, d6), (a54, b4, c1, d7), (a54, b4, c1, d8), (a54, b4, c1, d9), (a54,b4, c1, d10), (a54, b4, c1, dl), (a54, b4, c1, d12), (a54, b4, c1, d13),(a54, b4, c1, d14), (a54, b4, c1, d15), (a54, b4, c1, d16), (a54, b4,c1, d17), (a54, b4, c1, d18), (a54, b4, c1, d19), (a54, b4, c1, d20),(a54, b4, c1, d21), (a54, b4, c1, d22), (a54, b4, c2, d1), (a54, b4, c2,d2), (a54, b4, c2, d3), (a54, b4, c2, d4), (a54, b4, c2, d5), (a54, b4,c2, d6), (a54, b4, c2, d7), (a54, b4, c2, d8), (a54, b4, c2, d9), (a54,b4, c2, d10), (a54, b4, c2, d1), (a54, b4, c2, d12), (a54, b4, c2, d13),(a54, b4, c2, d14), (a54, b4, c2, d15), (a54, b4, c2, d16), (a54, b4,c2, d17), (a54, b4, c2, d18), (a54, b4, c2, d19), (a54, b4, c2, d20),(a54, b4, c2, d21), (a54, b4, c2, d22), (a54, b4, c3, d1), (a54, b4, c3,d2), (a54, b4, c3, d3), (a54, b4, c3, d4), (a54, b4, c3, d5), (a54, b4,c3, d6), (a54, b4, c3, d7), (a54, b4, c3, d8), (a54, b4, c3, d9), (a54,b4, c3, d10), (a54, b4, c3, d11), (a54, b4, c3, d2), (a54, b4, c3, d3),(a54, b4, c3, d14), (a54, b4, c3, d15), (a54, b4, c3, d16), (a54, b4,c3, d17), (a54, b4, c3, d18), (a54, b4, c3, d19), (a54, b4, c3, d20),(a54, b4, c3, d21), (a54, b4, c3, d22), (a54, b5, c1, d1), (a54, b5, c1,d2), (a54, b5, c1, d3), (a54, b5, c1, d4), (a54, b5, c1, d5), (a54, b5,c1, d6), (a54, b5, c1, d7), (a54, b5, c1, d8), (a54, b5, c1, d9), (a54,b5, c1, d10), (a54, b5, c1, d11), (a54, b5, c1, d12), (a54, b5, c1,d13), (a54, b5, c1, d14), (a54, b5, c1, d15), (a54, b5, c1, d16), (a54,b5, c1, d17), (a54, b5, c1, d18), (a54, b5, c1, d19), (a54, b5, c1,d20), (a54, b5, c1, d21), (a54, b5, c1, d22), (a54, b5, c2, d1), (a54,b5, c2, d2), (a54, b5, c2, d3), (a54, b5, c2, d4), (a54, b5, c2, d5),(a54, b5, c2, d6), (a54, b5, c2, d7), (a54, b5, c2, d8), (a54, b5, c2,d9), (a54, b5, c2, d10), (a54, b5, c2, d11), (a54, b5, c2, d12), (a54,b5, c2, d13), (a54, b5, c2, d14), (a54, b5, c2, d15), (a54, b5, c2,d16), (a54, b5, c2, d17), (a54, b5, c2, d18), (a54, b5, c2, d19), (a54,b5, c2, d20), (a54, b5, c2, d21), (a54, b5, c2, d22), (a54, b5, c3, d1),(a54, b5, c3, d2), (a54, b5, c3, d3), (a54, b5, c3, d4), (a54, b5, c3,d5), (a54, b5, c3, d6), (a54, b5, c3, d7), (a54, b5, c3, d8), (a54, b5,c3, d9), (a54, b5, c3, d10), (a54, b5, c3, d11), (a54, b5, c3, d12),(a54, b5, c3, d13), (a54, b5, c3, d14), (a54, b5, c3, d15), (a54, b5,c3, d6), (a54, b5, c3, d17), (a54, b5, c3, d6), (a54, b5, c3, d19),(a54, b5, c3, d20), (a54, b5, c3, d21), (a54, b5, c3, d22), (a54, b6,c1, d1), (a54, b6, c1, d2), (a54, b6, c1, d3), (a54, b6, c1, d4), (a54,b6, c1, d5), (a54, b6, c1, d6), (a54, b6, c1, d7), (a54, b6, c1, d8),(a54, b6, c1, d9), (a54, b6, c1, d10), (a54, b6, c1, d11), (a54, b6, c1,d12), (a54, b6, c1, d13), (a54, b6, c1, d14), (a54, b6, c1, d15), (a54,b6, c1, d16), (a54, b6, c1, d17), (a54, b6, c1, d18), (a54, b6, c1,d19), (a54, b6, c1, d20), (a54, b6, c1, d21), (a54, b6, c1, d22), (a54,b6, c2, d1), (a54, b6, c2, d2), (a54, b6, c2, d3), (a54, b6, c2, d4),(a54, b6, c2, d5), (a54, b6, c2, d6), (a54, b6, c2, d7), (a54, b6, c2,d8), (a54, b6, c2, d9), (a54, b6, c2, d10), (a54, b6, c2, d11), (a54,b6, c2, d12), (a54, b6, c2, d13), (a54, b6, c2, d14), (a54, b6, c2,d15), (a54, b6, c2, d16), (a54, b6, c2, d17), (a54, b6, c2, d18), (a54,b6, c2, d19), (a54, b6, c2, d20), (a54, b6, c2, d21), (a54, b6, c2,d22), (a54, b6, c3, d1), (a54, b6, c3, d2), (a54, b6, c3, d3), (a54, b6,c3, d4), (a54, b6, c3, d5), (a54, b6, c3, d6), (a54, b6, c3, d7), (a54,b6, c3, d8), (a54, b6, c3, d9), (a54, b6, c3, d10), (a54, b6, c3, d11),(a54, b6, c3, d12), (a54, b6, c3, d13), (a54, b6, c3, d14), (a54, b6,c3, d15), (a54, b6, c3, d16), (a54, b6, c3, d17), (a54, b6, c3, d18),(a54, b6, c3, d19), (a54, b6, c3, d20) (a54, b6, c3, d21), (a54, b6, c3,d22), (a55, b1, c1, d1), (a55, b1, c1, d2), (a55, b1, c1, d3), (a55, b1,c1, d4), (a55, b1, c1, d5), (a55, b1, c1, d6), (a55, b1, c1, d7), (a55,b1, c1, d3), (a55, b1, c1, d9), (a55, b1, c1, d10), (a55, b1, c1, d11),(a55, b1, c1, d12), (a55, b1, c1, d13), (a55, b1, c1, d14), (a55, b1,c1, d15), (a55, b1, c1, d16), (a55, b1, c1, d17), (a55, b1, c1, d13),(a55, b1, c1, d19), (a55, b1, c1, d20), (a55, b1, c1, d21), (a55, b1,c1, d22), (a55, b1, c2, d1), (a55, b1, c2, d2), (a55, b1, c2, d3), (a55,b1, c2, d4), (a55, b1, c2, d5), (a55, b1, c2, d6), (a55, b1, c2, d7),(a55, b1, c2, d8), (a55, b1, c2, d9), (a55, b1, c2, d10), (a55, b1, c2,d11), (a55, b1, c2, d12), (a55, b1, c2, d13), (a55, b1, c2, d14), (a55,b1, c2, d15), (a55, b1, c2, d16), (a55, b1, c2, d17), (a55, b1, c2,d18), (a55, b1, c2, d19), (a55, b1, c2, d20), (a55, b1, c2, d21), (a55,b1, c2, d22), (a55, b1, c3, d1), (a35, b1, c3, d2), (a55, b1, c3, d3),(a55, b1, c3, d4), (a55, b1, c3, d5), (a55, b1, c3, d6), (a55, b1, c3,d7), (a55, b1, c3, d8), (a55, b1, c3, d9), (a55, b1, c3, d10), (a55, b1,c3, d11), (a55, b1, c3, d12), (a55, b1, c3, d13), (a55, b1, c3, d14),(a55, b1, c3, d15), (a55, b1, c3, d16), (a55, b1, c3, d17), (a55, b1,c3, d18), (a55, b1, c3, d19), (a55, b1, c3, d20), (a55, b1, c3, d21),(a55, b1, c3, d22), (a55, b2, c1, d1), (a55, b2, c1, d2), (a55, b2, c1,d3), (a55, b2, c1, d4), (a55, b2, c1, d5), (a55, b2, c1, d6), (a55, b2,c1, d7), (a55, b2, c1, d8), (a55, b2, c1, d9), (a55, b2, c1, d10), (a55,b2, c1, d11), (a55, b2, c1, d12), (a55, b2, c1, d13), (a55, b2, c1,d14), (a55, b2, c1, d15), (a55, b2, c1, d16), (a55, b2, c1, d17), (a55,b2, c1, d18), (a55, b2, c1, d19), (a55, b2, c1, d20), (a55, b2, c1,d21), (a55, b2, c1, d22), (a55, b2, c2, d1), (a55, b2, c2, d2), (a55,b2, c2, d3), (a55, b2, c2, d4), (a55, b2, c2, d5), (a55, b2, c2, d6),(a55, b2, c2, d7), (a55, b2, c2, d8), (a55, b2, c2, d9), (a55, b2, c2,d10), (a55, b2, c2, d11), (a55, b2, c2, d12), (a55, b2, c2, d13), (a55,b2, c2, d14), (a55, b2, c2, d15), (a55, b2, c2, d16), (a55, b2, c2,d17), (a55, b2, c2, d18), (a55, b2, c2, d19), (a55, b2, c2, d20), (a55,b2, c2, d21), (a55, b2, c2, d22), (a55, b2, c3, d1), (a55, b2, c3, d2),(a55, b2, c3, d3), (a55, b2, c3, d4), (a55, b2, c3, d5), (a55, b2, c3,d6), (a55, b2, c3, d7), (a55, b2, c3, d8), (a55, b2, c3, d9), (a55, b2,c3, d10), (a55, b2, c3, d11), (a55, b2, c3, d12), (a55, b2, c3, d13),(a55, b2, c3, d14), (a55, b2, c3, d15), (a55, b2, c3, d16), (a55, b2,c3, d17), (a55, b2, c3, d18), (a55, b2, c3, d19), (a55, b2, c3, d20),(a55, b2, c3, d21), (a55, b2, c3, d22), (a55, b3, c1, d1), (a55, b3, c1,d2), (a55, b3, c1, d3), (a55, b3, c1, d4), (a55, b3, c1, d5), (a55, b3,c1, d6), (a55, b3, c1, d7), (a55, b3, c1, d8), (a55, b3, c1, d9), (a55,b3, c1, d10), (a55, b3, c1, d11), (a55, b3, c1, d12), (a55, b3, c1,d13), (a55, b3, c1, d14), (a55, b3, c1, d15), (a55, b3, c1, d16), (a55,b3, c1, d17), (a55, b3, c1, d18), (a55, b3, c1, d19), (a55, b3, c1,d20), (a55, b3, c1, d21), (a55, b3, c1, d22), (a55, b3, c2, d1), (a55,b3, c2, d2), (a55, b3, c2, d3), (a55, b3, c2, d4), (a55, b3, c2, d5),(a55, b3, c2, d6), (a55, b3, c2, d7), (a55, b3, c2, d8), (a55, b3, c2,d9), (a55, b3, c2, d10), (a55, b3, c2, d1), (a55, b3, c2, d2), (a55, b3,c2, d13), (a55, b3, c2, d14), (a5, b3, c2, d15), (a55, b3, c2, d16),(a55, b3, c2, d17), (a55, b3, c2, d18), (a55, b3, c2, d19), (a55, b3,c2, d20), (a55, b3, c2, d21), (a55, b3, c2, d22), (a55, b3, c3, d1),(a55, b3, c3, d2), (a55, b3, c3, d3), (a55, b3, c3, d4), (a55, b3, c3,d5), (a55, b3, c3, d6), (a55, b3, c3, d7), (a55, b3, c3, d8), (a55, b3,c3, d9), (a55, b3, c3, d10), (a55, b3, c3, d11), (a55, b3, c3, d12),(a55, b3, c3, d13), (a55, b3, c3, d14), (a55, b3, c3, d15), (a55, b3,c3, d6), (a55, b3, c3, d17), (a55, b3, c3, d18), (a55, b3, c3, d19),(a55, b3, c3, d20), (a55, b3, c3, d21), (a55, b3, c3, d22), (a55, b4,c1, d1), (a55, b4, c1, d2), (a55, b4, c1, d3), (a55, b4, c1, d4), (a55,b4, c1, d5), (a55, b4, c1, d6), (a55, b4, c1, d7), (a55, b4, c1, d8),(a55, b4, c1, d9), (a55, b4, c1, d10), (a55, b4, c1, d11), (a55, b4, c1,d12), (a55, b4, c1, d13), (a55, b4, c1, d14), (a55, b4, c1, d15), (a55,b4, c1, d16), (a55, b4, c1, d17), (a55, b4, c1, d18), (a55, b4, c1,d19), (a55, b4, c1, d20), (a55, b4, c1, d21), (a55, b4, c1, d22), (a55,b4, c2, d1), (a55, b4, c2, d2), (a55, b4, c2, d3), (a55, b4, c2, d4),(a55, b4, c2, d5), (a55, b4, c2, d6), (a55, 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d20), (a56,b4, c1, d21), (a56, b4, c1, d22), (a56, b4, c2, d1), (a56, b4, c2, d2),(a56, b4, c2, d3), (a56, b4, c2, d4), (a56, b4, c2, d5), (a56, b4, c2,d6), (a56, b4, c2, d7), (a56, b4, c2, d8), (a56, b4, c2, d9), (a56, b4,c2, d10), (a56, b4, c2, d11), (a56, b4, c2, d12), (a56, b4, c2, d13),(a56, b4, c2, d14), (a56, b4, c2, d15), (a56, b4, c2, d16), (a56, b4,c2, d17), (a56, b4, c2, d18), (a56, b4, c2, d19), (a56, b4, c2, d20),(a56, b4, c2, d21), (a56, b4, c2, d22), (a56, b4, c3, d1), (a56, b4, c3,d2), (a56, b4, c3, d3), (a53, b4, c3, d4), (a56, b4, c3, d5), (a56, b4,c3, d6), (a56, b4, c3, d7), (a56, b4, c3, d8), (a56, b4, c3, d9), (a56,b4, c3, d10), (a56, b4, c3, d11), (a56, b4, c3, d12), (a56, b4, c3,d13), (a56, b4, c3, d14), (a56, b4, c3, d15), (a56, b4, c3, d16), (a56,b4, c3, d17), (a56, b4, c3, d18), (a56, b4, c3, d19), (a56, b4, c3,d20), (a56, b4, c3, d21), (a56, b4, c3, d22), (a56, b5, c1, d1), (a56,b5, c1, d2), (a56, b5, c1, d3), (a56, b5, c1, d4), (a56, b5, c1, d5),(a56, b5, c1, d6), (a56, b5, c1, d7), (a56, b5, c1, d8), (a56, b5, c1,d9), (a56, b5, c1, d10), (a56, b5, c1, d11), (a56, b5, c1, d12), (a56,b5, c1, d13), (a56, b5, c1, d14), (a56, b5, c1, d15), (a56, b5, c1,d16), (a56, b5, c1, d17), (a56, b5, c1, d18), (a56, b5, c1, d19), (a56,b5, c1, d20), (a56, b5, c1, d21), (a56, b5, c1, d22), (a56, b5, c2, d1),(a56, b5, c2, d2), (a56, b5, c2, d3), (a56, b5, c2, d4), (a56, b5, c2,d5), (a56, b5, c2, d6), (a56, b5, c2, d7), (a56, b5, c2, d8), (a56, b5,c2, d9), (a56, b5, c2, d10), (a56, b5, c2, d11), (a56, b5, c2, d12),(a56, b5, c2, d13), (a56, b5, c2, d14), (a56, b5, c2, d15), (a56, b5,c2, d16), (a56, b5, c2, d17), (a56, b5, c2, d18), (a56, b5, c2, d19),(a56, b5, c2, d20), (a56, b5, c2, d21), (a56, b5, c2, d22), (a56, b5,c3, d1), (a56, b5, c3, d2), (a56, b5, c3, d3), (a56, b5, c3, d4), (a56,b5, c3, d5), (a56, b5, c3, d6), (a56, b5, c3, d7), (a56, b5, c3, d8),(a56, b5, c3, d9), (a56, b5, c3, d10), (a56, b5, c3, d11), (a56, b5, c3,d12), (a56, b5, c3, d13), (a56, 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d21), (a56, b6,c2, d22), (a56, b6, c3, d1), (a56, b6, c3, d2), (a56, b6, c3, d3), (a56,b6, c3, d4), (a56, b6, c3, d5), (a56, b6, c3, d6), (a56, b6, c3, d7),(a56, b6, c3, d8), (a56, b6, c3, d19), (a56, b6, c3, d10), (a56, b6, c3,d11), (a56, b6, c3, d12), (a56, b6, c3, d13), (a56, b6, c3, d14), (a56,b6, c3, d15), (a56, b6, c3, d16), (a56, b6, c3, d17), (a56, b6, c3,d18), (a56, b6, c3, d19), (a56, b6, c3, d20), (a56, b6, c3, d21), (a56,b6, c3, d22), (a57, b1, c1, d1), (a57, b1, c1, d2), (a57, b1, c1, d3),(a57, b1, c1, d4), (a57, b1, c1, d5), (a57, b1, c1, d6), (a37, b1, c1,d7), (a57, b1, c1, d8), (a57, b1, c1, d9), (a57, b1, c1, d10), (a57, b1,c1, d11), (a57, b1, c1, d12), (a57, b1, c1, d13), (a57, b1, c1, d14),(a57, b1, c1, d15), (a57, b1, c1, d16), (a51, b1, c1, d17), (a57, b1,c1, d18), (a57, b1, c1, d19), (a7, b1, c1, d20), (a57, b1, c1, d21),(a57, b1, c1, d22), (a57, b1, c2, d1), (a57, b1, c2, d2), (a57, b1, c2,d3), (a57, b1, c2, d4), (a37, b1, c2, d5), (a57, b1, c2, d6), (a57, b1,c2, d7), (a57, b1, c2, d8), (a57, b1, c2, d9), (a57, b1, c2, d10), (a57,b1, c2, d11), (a57, b1, c2, d12), (a57, b1, c2, d13), (a57, b1, c2,d14), (a57, b1, c2, d15), (a57, b1, c2, d16), (a57, b1, c2, d17), (a57,b1, c2, d18), (a57, b1, c2, d19), (a57, b1, c2, d20), (a57, b1, c2,d21), (a57, b1, c2, d22), (a57, b1, c3, d1), (a57, b1, c3, d2), (a57,b1, c3, d3), (a57, b1, c3, d4), (a57, b1, c3, d5), (a57, b1, c3, d6),(a57, b1, c3, d7), (a57, b1, c3, d8), (a57, b1, c3, d9), (a57, b1, c3,d10), (a57, b1, c3, d11), (a57, b1, c3, d12), (a57, b1, c3, d13), (a57,b1, c3, d14), (a57, b1, c3, d15), (a57, b1, c3, d16), (a57, b1, c3,d17), (a57, b1, c3, d18), (a57, b1, c3, d19), (a57, b1, c3, d20), (a57,b1, c3, d21), (a57, b1, c3, d22), (a57, b2, c1, d1), (a57, b2, c1, d2),(a57, b2, c1, d3), (a57, b2, c1, d4), (a57, b2, c1, d5), (a57, b2, c1,d6), (a57, b2, c1, d7), (a57, b2, c1, d8), (a57, b2, c1, d9), (a57, b2,c1, d10), (a57, b2, c1, d11), (a57, b2, c1, d12), (a57, b2, c1, d13),(a57, b2, c1, d14), (a57, b2, c1, d15), (a57, b2, c1, d16), (a57, b2,c1, d17), (a57, b2, c1, d18), (a57, b2, c1, d19), (a57, b2, c1, d20),(a57, b2, c1, d21), (a57, b2, c1, d22), (a57, b2, c2, d1), (a57, b2, c2,d2), (a57, b2, c2, d3), (a57, b2, c2, d4), (a57, b2, c2, d5), (a57, b2,c2, d6), (a57, b2, c2, d7), (a57, b2, c2, d8), (a57, b2, c2, d9), (a57,b2, c2, d10), (a57, b2, c2, d11), (a57, b2, c2, d12), (a57, b2, c2,d13), (a57, b2, c2, d14), (a57, b2, c2, d15), (a57, b2, c2, d16), (a57,b2, c2, d17), (a57, b2, c2, d18), (a57, b2, c2, d19), (a57, b2, c2,d20), (a57, b2, c2, d21), (a57, b2, c2, d22), (a57, b2, c3, d1), (a57,b2, c3, d2), (a57, b2, c3, d3), (a57, b2, c3, d4), (a57, b2, c3, d5),(a5, b2, c3, d6), (a57, b2, c3, d7), (a57, b2, c3, d8), (a57, b2, c3,d9), (a57, b2, c3, d10), (a57, b2, c3, d11), (a57, b2, c3, d12), (a57,b2, c3, d13), (a57, b2, c3, d14), (a57, b2, c3, d15), (a57, b2, c3,d16), (a57, b2, c3, d17), (a57, b2, c3, d18), (a57, b2, c3, d19), (a57,b2, c3, d20), (a57, b2, c3, d21), (a57, b2, c3, d22), (a57, b3, c1, d1),(a57, b3, c1, d2), (a57, b3, c1, d3), (a57, b3, c1, d4), (a57, b3, c1,d5), (a57, b3, c1, d6), (a57, b3, c1, d7), (a57, b3, c1, d8), (a57, b3,c1, d9), (a57, b3, c1, d10), (a57, b3, c1, d11), (a57, b3, c1, d12),(a57, b3, c1, d13), (a57, b3, c1, d14), (a57, b3, c1, d15), (a57, b3,c1, d16), (a57, b3, c1, d17), (a57, b3, c1, d18), (a57, b3, c1, d19),(a57, b3, c1, d20), (a57, b3, c1, d21), (a57, b3, c1, d22), (a57, b3,c2, d1), (a57, b3, c2, d2), (a57, b3, c2, d3), (a57, b3, c2, d4), (a57,b3, c2, d5), (a57, b3, c2, d6), (a57, b3, c2, d7), (a57, b3, c2, d8),(a57, b3, c2, d9), (a57, b3, c2, d10), (a57, b3, c2, d11), (a57, b3, c2,d12), (a57, b3, c2, d13), (a57, b3, c2, d14), (a57, b3, c2, d15), (a57,b3, c2, d16), (a57, b3, c2, d17), (a57, b3, c2, d18), (a57, b3, c2,d19), (a57, b3, c2, d20), (a57, b3, c2, d21), (a57, b3, c2, d22), (a57,b3, c3, d1), (a57, b3, c3, d2), (a57, b3, c3, d3), (a57, b3, c3, d4),(a57, b3, c3, d5), (a57, b3, c3, d6), (a57, b3, c3, d7), (a57, b3, c3,d8), (a57, b3, c3, d9), (a57, b3, c3, d10), (a57, b3, c3, d11), (a57,b3, c3, d12), (a57, b3, c3, d13), (a57, b3, c3, d14), (a57, b3, c3,d15), (a57, b3, c3, d16), (a57, b3, c3, d17), (a57, b3, c3, d18), (a57,b3, c3, d19), (a57, b3, c3, d20), (a57, b3, c3, d21), (a57, b3, c3,d22), (a57, b4, c1, d1), (a57, b4, c1, d2), (a57, b4, c1, d3), (a57, b4,c1, d4), (a57, b4, c1, d5), (a57, b4, c1, d6), (a57, b4, c1, d7), (a57,b4, c1, d8), (a57, b4, c1, d9), (a57, b4, c1, d10), (a57, b4, c1, d11),(a57, b4, c1, d12), (a57, b4, c1, d13), (a57, b4, c1, d14), (a57, b4,c1, d15), (a57, b4, c1, d16), (a57, b4, c1, d17), (a57, b4, c1, d18),(a57, b4, c1, d19), (a57, b4, c1, d20), (a57, b4, c1, d21), (a57, b4,c1, d22), (a57, b4, c2, d1), (a57, b4, c2, d2), (a57, b4, c2, d3), (a57,b4, c2, d4), (a57, b4, c2, d5), (a57, b4, c2, d6), (a57, b4, c2, d7),(a57, b4, c2, d5), (a57, b4, c2, d9), (a57, b4, c2, d10), (a57, b4, c2,d11), (a57, b4, c2, d12), (a57, b4, c2, d13), (a57, b4, c2, d14), (a57,b4, c2, d15), (a57, b4, c2, d16), (a57, b4, c2, d17), (a57, b4, c2,d18), (a57, b4, c2, d19), (a57, b4, c2, d20), (a57, b4, c2, d21), (a57,b4, c2, d22), (a57, b4, c3, d), (a57, b4, c3, d2), (a57, b4, c3, d3),(a57, b4, c3, d4), (a57, b4, c3, d5), (a57, b4, c3, d6), (a57, b4, c3,d7), (a57, b4, c3, d8), (a57, b4, c3, d9), (a57, b4, c3, d10), (a57, b4,c3, d11), (a57, b4, c3, d12), (a57, b4, c3, d13), (a57, b4, c3, d14),(a57, b4, c3, d15), (a57, b4, c3, d16), (a57, b4, c3, d17), (a57, b4,c3, d18), (a57, b4, c3, d19), (a57, b4, c3, d20), (a57, b4, c3, d21),(a57, b4, c3, d22), (a57, b5, c1, d1), (a57, b5, c7, d2), (a57, b5, c1,d3), (a57, b5, c1, d4), (a57, b5, c1, d5), (a57, b5, c1, d6), (a57, b5,c1, d7), (a57, b5, c1, d8), (a57, b5, c1, d9), (a57, b5, c1, d10), (a57,b5, c1, d11), (a57, b5, c1, d12), (a57, b5, c1, d13), (a57, b5, c1,d14), (a57, b5, c1, d15), (a57, b5, c1, d16), (a57, b5, c1, d17), (a57,b5, c1, d18), (a57, b5, c1, d19), (a57, b5, c1, d20), (a57, b5, c1,d21), (a57, b5, c1, d22), (a57, b5, c2, d1), (a57, b5, c2, d2), (a57,b5, c2, d3), (a57, b5, c2, d4), (a57, b5, c2, d5), (a57, b5, c2, d6),(a57, b5, c2, d7), (a57, b5, c2, d8), (a57, b5, c2, d9), (a57, b5, c2,d10), (a57, b5, c2, d11), (a57, b5, c2, d12), (a57, b5, c2, d13), (a57,b5, c2, d14), (a57, b5, c2, d15), (a57, b5, c2, d16), (a57, b5, c2,d17), (a57, b5, c2, d18), (a57, b5, c2, d19), (a57, b5, c2, d20), (a57,b5, c2, d21), (a57, b5, c2, d22), (a57, b5, c3, d1), (a57, b5, c3, d2),(a57, b5, c3, d3), (a57, b5, c3, d4), (a57, b5, c3, d5), (a57, b5, c3,d6), (a57, b5, c3, d7), (a57, b5, c3, d8), (a57, b5, c3, d9), (a57, b5,c3, d10), (a57, b5, c3, d11), (a57, b5, c3, d12), (a57, b5, c3, d13),(a57, b5, c3, d14), (a57, b5, c3, d15), (a57, b5, c3, d16), (a57, b5,c3, d17), (a57, b5, c3, d18), (a57, b5, c3, d19), (a57, b5, c3, d20),(a57, b5, c3, d21), (a57, b5, c3, d22), (a57, b6, c1, d1), (a57, b6, c1,d2), (a57, b6, c1, d3), (a57, b6, c1, d4), (a57, b6, c1, d5), (a57, b6,c1, d6), (a57, b6, c1, d7), (a57, b6, c1, d8), (a57, b6, c1, d9), (a57,b6, c1, d10), (a57, b6, c1, d11), (a57, b6, c1, d12), (a57, b6, c1,d13), (a57, b6, c1, d14), (a57, b6, c1, d15), (a57, b6, c1, d16), (a57,b6, c1, d17), (a57, b6, c1, d18), (a57, b6, c1, d19), (a57, b6, c1,d20), (a57, b6, c1, d21), (a57, b6, c1, d22), (a57, b6, c2, d1), (a57,b6, c2, d2), (a57, b6, c2, d3), (a57, b6, c2, d4), (a57, b6, c2, d5),(a57, b6, c2, d6), (a57, b6, c2, d7), (a57, b6, c2, d8), (a57, b6, c2,d9), (a57, b6, c2, d10), (a57, b6, c2, d11), (a57, b6, c2, d12), (a57,b6, c2, d13), (a57, b6, c2, d14), (a57, b6, c2, d15), (a57, b6, c2,d16), (a57, b6, c2, d17), (a57, b6, c2, d18), (a57, b6, c2, d19), (a57,b6, c2, d20), (a57, b6, c2, d21), (a57, b6, c2, d22), (a57, b6, c3, d1),(a57, b6, c3, d2), (a57, b6, c3, d3), (a57, b6, c3, d4), (a57, b6, c3,d5), (a57, b6, c3, d6), (a57, b6, c3, d7), (a57, b6, c3, d8), (a57, b6,c3, d9), (a57, b6, c3, d10), (a57, b6, c3, d11), (a57, b6, c3, d12),(a57, b6, c3, d13), (a57, b6, c3, d14), (a57, b6, c3, d15), (a57, b6,c3, d16), (a57, b6, c3, d17), (a57, b6, c3, d18), (a57, b6, c3, d19),(a57, b6, c3, d20), (a57, b6, c3, d21), (a57, b6, c3, d22), (a58, b1,c1, d1), (a58, b1, c1, d2), (a58, b1, c1, d3), (a58, b1, c1, d4), (a58,b1, c1, d5), (a58, b1, c1, d6), (a58, b1, c1, d7), (a58, b1, c1, d8),(a58, b1, c1, d9), (a58, b1, c1, d10), (a58, b1, c1, d11), (a58, b1, c1,d12), (a58, b1, c1, d13), (a58, b1, c1, d14), (a58, b1, c1, d15), (a58,b1, c1, d16), (a58, b1, c1, d17), (a55, b1, c1, d18), (a58, b1, c1,d19), (a58, b1, c1, d20), (a58, b1, c1, d21), (a58, b1, c1, d22), (a58,b1, c2, d1), (a58, b1, c2, d2), (a58, b1, c2, d3), (a58, b1, c2, d4),(a58, b1, c2, d5), (a58, b1, c2, d6), (a58, b1, c2, d7), (a58, b1, c2,d8), (a58, b1, c2, d9), (a58, b1, c2, d10), (a58, b1, c2, d11), (a58,b1, c2, d12), (a58, b1, c2, d13), (a58, b1, c2, d14) (a58, b1, c2, d15),(a58, b1, c2, d16), (a58, b1, c2, d17), (a58, b1, c2, d18), (a58, b1,c2, d19), (a58, b1, c2, d20), (a58, b1, c2, d21), (a58, b1, c2, d22),(a58, b1, c3, d1), (a58, b1, c3, d2), (a58, b1, c3, d3), (a58, b1, c3,d4), (a58, b1, c3, d5), (a58, b1, c3, d6), (a58, b1, c3, d7), (a58, b1,c3, d8), (a58, b1, c3, d9), (a58, b1, c3, d10), (a58, b1, c3, d11),(a58, b, c3, d12), (a58, b1, c3, d13), (a58, b1, c3, d14), (a58, b1, c3,d15), (a58, b1, c3, d16), (a58, b1, c3, d17), (a58, b1, c3, d18), (a58,b1, c3, d19), (a58, b1, c3, d20), (a58, b1, c3, d21), (a58, b1, c3,d22), (a58, b2, c1, d1), (a58, b2, c1, d2), (a58, b2, c1, d3), (a58, b2,c1, d4), (a58, b2, c1, d5), (a58, b2, c1, d6), (a58, b2, c1, d7), (a58,b2, c1, d8), (a58, b2, c1, d9), (a58, b2, c1, d10), (a58, b2, c1, d11),(a58, b2, c1, d12), (a58, b2, c1, d13), (a58, b2, c1, d14), (a58, b2,c1, d15), (a58, b2, c1, d16), (a58, b2, c1, d17), (a58, b2, c1, d18),(a58, b2, c1, d19), (a58, b2, c1, d20), (a58, b2, c1, d21), (a58, b2,c1, d22), (a55, b2, c2, d1), (a58, b2, c2, d2), (a58, b2, c2, d3), (a58,b2, c2, d4), (a58, b2, c2, d5), (a58, b2, c2, d6), (a58, b2, c2, d7),(a58, b2, c2, d8), (a58, b2, c2, d9), (a58, b2, c2, d10), (a58, b2, c2,d11), (a58, b2, c2, d12), (a58, b2, c2, d13), (a58, b2, c2, d14), (a58,b2, c2, d15), (a58, b2, c2, d16), (a58, b2, c2, d17), (a58, b2, c2,d18), (a58, b2, c2, d19), (a58, b2, c2, d20), (a58, b2, c2, d21), (a58,b2, c2, d22), (a58, b2, c3, d1), (a58, b2, c3, d2), (a58, b2, c3, d3),(a58, b2, c3, d4), (a58, b2, c3, d5), (a58, b2, c3, d6), (a58, b2, c3,d7), (a58, b2, c3, d8), (a58, b2, c3, d9), (a58, b2, c3, d10), (a58, b2,c3, d11), (a58, b2, c3, d12), (a58, b2, c3, d13), (a58, b2, c3, d14),(a58, b2, c3, d15), (a58, b2, c3, d6), (a58, b2, c3, d17), (a58, b2, c3,d18), (a58, b2, c3, d19), (a58, b2, c3, d20), (a58, b2, c3, d21), (a58,b2, c3, d22), (a58, b3, c1, d1), (a58, b3, c1, d2), (a58, b3, c1, d3),(a58, b3, c1, d4), (a58, b3, c1, d5), (a58, b3, c1, d6), (a58, b3, c1,d7), (a58, b3, c1, d8), (a58, b3, c1, d9), (a58, b3, c1, d10), (a58, b3,c1, d11), (a58, b3, c1, d12), (a58, b3, c1, d13), (a58, b3, c1, d14),(a58, b3, c1, d15), (a58, b3, c1, d16), (a58, b3, c1, d7), (a58, b3, c1,d18), (a58, b3, c1, d19), (a58, b3, c1, d20), (a58, b3, c1, d21), (a58,b3, c1, d22), (a58, b3, c2, d1), (a58, b3, c2, d2), (a58, b3, c2, d3),(a58, b3, c2, d4), (a58, b3, c2, d5), (a58, b3, c2, d6), (a58, b3, c2,d7), (a58, b3, c2, d8), (a58, b3, c2, d9), (a58, b3, c2, d10), (a58, b3,c2, d11), (a58, b3, c2, d12), (a58, b3, c2, d13), (a58, b3, c2, d14),(a58, b3, c2, d15), (a58, b3, c2, d16), (a58, b3, c2, d17), (a58, b3,c2, d18), (a58, b3, c2, d19), (a58, b3, c2, d20), (a58, b3, c2, d21),(a58, b3, c2, d22), (a58, b3, c3, d1), (a58, b3, c3, d2), (a58, b3, c3,d3), (a58, b3, c3, d4), (a58, b3, c3, d5), (a58, b3, c3, d6), (a58, b3,c3, d7), (a58, b3, c3, d8), (a58, b3, c3, d9), (a58, b3, c3, d10), (a58,b3, c3, d11), (a58, b3, c3, d12), (a58, b3, c3, d13), (a58, b3, c3,d14), (a58, b3, c3, d15), (a58, b3, c3, d16), (a58, b3, c3, d17), (a58,b3, c3, d18), (a58, b3, c3, d19), (a58, b3, c3, d20), (a58, b3, c3,d21), (a58, b3, c3, d22), (a58, b4, c1, d1), (a58, b4, c1, d2), (a58,b4, c1, d3), (a58, b4, c1, d4), (a58, b4, c1, d5), (a58, b4, c1, d6),(a58, b4, c1, d7), (a58, b4, c1, d8), (a58, b4, c1, d9), (a58, b4, c1,d10), (a58, b4, c1, d11), (a58, b4, c1, d12), (a58, b4, c1, d13), (a58,b4, c1, d14), (a58, b4, c1, d15), (a58, b4, c1, d16), (a58, b4, c1,d17), (a58, b4, c1, d18), (a58, b4, c1, d19), (a58, b4, c1, d20), (a58,b4, c1, d21), (a58, b4, c1, d22), (a58, b4, c2, d1), (a58, b4, c2, d2),(a58, b4, c2, d3), (a58, b4, c2, d4), (a58, b4, c2, d5), (a58, b4, c2,d6), (a58, b4, c2, d7), (a58, b4, c2, d8), (a58, b4, c2, d9), (a58, b4,c2, d10), (a58, b4, c2, d11), (a58, b4, c2, d12), (a58, b4, c2, d13),(a58, b4, c2, d14), (a58, b4, c2, d15), (a58, b4, c2, d16), (a58, b4,c2, d17), (a58, b4, c2, d18), (a58, b4, c2, d19), (a58, b4, c2, d20),(a58, b4, c2, d21), (a58, b4, c2, d22), (a58, b4, c3, d1), (a58, b4, c3,d2), (a58, b4, c3, d3), (a58, b4, c3, d4), (a58, b4, c3, d5), (a58, b4,c3, d6), (a58, b4, c3, d7), (a58, b4, c3, d8), (a58, b4, c3, d9), (a58,b4, c3, d10), (a58, b4, c3, d11), (a58, b4, c3, d12), (a58, b4, c3,d13), (a58, b4, c3, d14), (a58, b4, c3, d15), (a58, b4, c3, d16), (a58,b4, c3, d17), (a58, b4, c3, d18), (a58, b4, c3, d19), (a58, b4, c3,d20), (a58, b4, c3, d21), (a58, b4, c3, d22), (a58, b5, c1, d1), (a58,b5, c1, d2), (a58, b5, c1, d3), (a58, b5, c1, d4), (a58, b5, c1, d5),(a58, b5, c1, d6), (a58, b5, c1, d7), (a58, b5, c1, d8), (a58, b5, c1,d9), (a58, b5, c1, d10), (a58, b5, c1, d11), (a58, b5, c1, d12), (a58,b5, c1, d13), (a58, b5, c1, d14), (a58, b5, c1, d15), (a58, b5, c1,d16), (a58, b5, c1, d17), (a58, b5, c1, d18), (a58, b5, c1, d19), (a58,b5, c1, d20), (a58, b5, c1, d21), (a58, b5, c1, d22), (a58, b5, c2, d1),(a58, b5, c2, d2), (a58, b5, c2, d3), (a58, b5, c2, d4), (a58, b5, c2,d5), (a58, b5, c2, d6), (a58, b5, c2, d7), (a58, b5, c2, d8), (a58, b5,c2, d9), (a58, b5, c2, d10), (a58, b5, c2, d11), (a58, b5, c2, d12),(a58, b5, c2, d13), (a58, b5, c2, d14), (a58, b5, c2, d15), (a58, b5,c2, d16), (a58, b5, c2, d17), (a58, b5, c2, d18), (a58, b5, c2, d19),(a58, b5, c2, d20), (a58, b5, c2, d21), (a58, b5, c2, d22), (a58, b5,c3, d1), (a58, b5, c3, d2), (a58, b5, c3, d3), (a58, b5, c3, d4), (a58,b5, c3, d5), (a58, b5, c3, d6), (a58, b5, c3, d7), (a58, b5, c3, d8),(a58, b5, c3, d9), (a58, b5, c3, d10), (a58, b5, c3, d11), (a58, b5, c3,d12), (a58, b5, c3, d13), (a58, b5, c3, d14), (a58, b5, c3, d15), (a58,b5, c3, d16), (a58, b5, c3, d17), (a58, b5, c3, d18), (a58, b5, c3,d19), (a58, b5, c3, d20), (a58, b5, c3, d21), (a58, b5, c3, d22), (a58,b6, c1, d1), (a58, b6, c1, d2), (a58, b6, c1, d3), (a58, b6, c1, d4),(a58, b6, c1, d5), (a58, b6, c1, d6), (a58, b6, c1, d7), (a58, b6, c1,d8), (a58, b6, c1, d9), (a58, b6, c1, d10), (a58, b6, c1, d11), (a58,b6, c1, d12), (a58, b6, c1, d13), (a58, b6, c1, d14), (a58, b6, c1,d15), (a58, b6, c1, d16), (a58, b6, c1, d17), (a58, b6, c1, d18), (a58,b6, c1, d19), (a58, b6, c1, d20), (a58, b6, c1, d21), (a58, b6, c1,d22), (a58, b6, c2, d1), (a58, b6, C2, d2), (a58, b6, c2, d3), (a58, b6,c2, d4), (a58, b6, c2, d5), (a58, b6, c2, d6), (a58, b6, c2, d7), (a58,b6, c2, d8), (a58, b6, c2, d9), (a58, b6, c2, d10), (a58, b6, c2, d11),(a58, b6, c2, d12), (a58, b6, c2, d13), (a58, b6, c2, d14), (a58, b6,c2, d15), (a58, b6, c2, d16), (a58, b6, c2, d17), (a58, b6, c2, d18),(a58, b6, c2, d19), (a58, b6, c2, d20), (a58, b6, c2, d21), (a58, b6,c2, d22), (a58, b6, c3, d1), (a58, b6, c3, d2), (a58, be, c3, d3), (a58,b6, c3, d4), (a58, b6, c3, d5), (a58, b6, c3, d6), (a58, b6, c3, d7),(a58, b6, c3, d8), (a58, b6, c3, d9), (a58, b6, c3, d10), (a58, be, c3,d11), (a58, b6, c3, d12), (a58, b6, c3, d13), (a58, b6, c3, d14), (a58,b6, c3, d15), (a58, b6, c3, d16), (a58, b6, c3, d17), (a58, b6, c3,(d18), (a58, b6, c3, d19), (a58, b6, c3, d20), (a58, b6, c3, d21), (a58,b6, c3, d22), (a59, b1, c1, d1), (a59, b1, c1, d2), (a59, b1, c1, d3),(a59, b1, c1, d4), (a59, b1, c1, d5), (a59, b1, c1, d6), (a59, b1, c1,d7), (a59, b1, c1, d8), (a59, b1, c1, d9), (a59, b1, c1, d10), (a59, b1,c1, d11), (a59, b1, c1, d12), (a59, b1, c1, d13), (a59, b1, c1, d14),(a59, b1, c1, d15), (a59, b1, c1, d16), (a59, b1, c1, d17), (a59, b1,c1, d18), (a59, b1, c1, d19), (a59, b1, c1, d20), (a59, b1, c1, d21),(a59, b1, c1, d22), (a59, b1, c2, d1), (a59, b1, c2, d2), (a59, b1, c2,d3), (a59, b1, c2, d4), (a59, b1, c2, d5), (a59, b1, c2, d6), (a59, b1,c2, d7), (a59, b1, c2, d8), (a59, b1, c2, d9), (a59, b1, c2, d10), (a59,b1, c2, d11), (a59, b1, c2, d12), (a59, b1, c2, d13), (a59, b1, c2,d14), (a59, b1, c2, d15), (a59, b1, c2, die), (a59, b1, c2, d17), (a59,b1, c2, d18), (a59, b1, c2, d19), (a59, b1, c2, d20), (a59, b1, c2,d21), (a59, b1, c2, d22), (a59, b1, c3, d1), (a59, b1, c3, d2), (a59,b1, c3, d3), (a59, b1, c3, d4), (a59, b1, c3, d5), (a59, b1, c3, d6),(a59, b1, c3, d7), (a59, b1, c3, d8), (a59, b1, c3, d9), (a59, b1, c3,d10), (a59, b1, c3, d11), (a59, b1, c3, d12), (a59, b1, c3, d13), (a59,b1, c3, d14), (a59, b1, c3, d15), (a59, b1, c3, d16), (a59, b1, c3,d17), (a59, b1, c3, d18), (a59, b1, c3, d19), (a59, b1, c3, d20), (a59,b1, c3, d21), (a59, b1, c3, d22), (a59, b2, c1, d1), (a59, b2, c1, d2),(a59, b2, c1, d3), (a59, b2, c1, d4), (a59, b2, c1, d5), (a59, b2, c1,d6), (a59, b2, c1, d7), (a59, b2, c1, d8), (a59, b2, c1, d9), (a59, b2,c1, d10), (a59, b2, c1, d11), (a59, b2, c1, d12), (a59, b2, c1, d13),(a59, b2, c1, d14), (a59, b2, c1, d15), (a59, b2, c1, d16), (a59, b2,c1, d17), (a59, b2, c1, d18), (a59, b2, c1, d19), (a59, b2, c1, d20),(a59, b2, c1, d21), (a59, b2, c1, d22), (a59, b2, c2, d1), (a59, b2, c2,d2), (a59, b2, c2, d3), (a59, b2, c2, d4), (a59, b2, c2, d5), (a59, b2,c2, d6), (a59, b2, c2, d7), (a59, b2, c2, d8), (a59, b2, c2, d9), (a59,b2, c2, d10), (a59, b2, c2, d11), (a59, b2, c2, d12), (a59, b2, c2,d13), (a59, b2, c2, d14), (a59, b2, c2, d15), (a59, b2, c2, d16), (a59,b2, c2, d17), (a55, b2, c2, d18), (a59, b2, c2, d19), (a59, b2, c2,d20), (a59, b2, c2, d21), (a59, b2, c2, d22), (a59, b2, c3, d1), (a59,b2, c3, d2), (a59, b2, c3, d3), (a59, b2, c3, d4), (a59, b2, c3, d5),(a59, b2, c3, d6), (a59, b2, c3, d7), (a59, b2, c3, d8), (a59, b2, c3,d9), (a59, b2, c3, d10), (a59, b2, c3, d11), (a59, b2, c3, d12), (a59,b2, c3, d13), (a59, b2, c3, d14), (a59, b2, c3, d15), (a59, c2, c3,d16), (a59, b2, c3, d17), (a59, b2, c3, d18), (a59, b2, c3, d19), (a59,b2, c3, d20), (a59, b2, c3, d21), (a59, b2, c3, d22), (a59, b3, c1, d1),(a59, b3, c1, d2), (a59, b3, c1, d3), (a59, b3, c1, d4), (a59, b3, c1,d5), (a59, b3, c1, d6), (a59, b3, c1, d7), (a59, b3, c1, d8), (a59, b3,c1, d9), (a59, b3, c1, d10), (a59, b3, c1, d11), (a59, b3, c1, d12),(a59, b3, c1, d13), (a59, b3, c1, d14), (a59, b3, c1, d15), (a59, b3,c1, d16), (a59, b3, c1, d17), (a59, b3, c1, d18), (a59, b3, c1, d19),(a59, b3, c1, d20), (a59, b3, c1, d21), (a59, b3, c1, d22), (a59, b3,c2, d1), (a59, b3, c2, d2), (a59, b3, c2, d3), (a59, b3, c2, d4), (a59,b3, c2, d5), (a59, b3, c2, d6), (a59, b3, c2, d7), (a59, b3, c2, d8),(a59, b3, c2, d9), (a59, b3, c2, d10), (a59, b3, c2, d11), (a59, b3, c2,d12), (a59, b3, c2, d13), (a59, b3, c2, d14), (a59, b3, c2, d15), (a59,b3, c2, d16), (a59, b3, c2, d17), (a59, b3, c2, d18), (a59, b3, c2,d19), (a59, b3, c2, d20), (a59, b3, c2, d21), (a59, b3, c2, d22), (a59,b3, c3, d1), (a59, b3, c3, d2), (a59, b3, c3, d3), (a59, b3, c3, d4),(a59, b3, c3, d5), (a59, b3, c3, d6), (a59, b3, c3, d7), (a59, b3, c3,d8), (a59, b3, c3, d9), (a59, b3, c3, d10), (a59, b3, c3, d11), (a59,b3, c3, d12), (a59, b3, c3, d13), (a59, b3, c3, d14), (a59, b3, c3,d15), (a59, b3, c3, d16), (a59, b3, c3, d17), (a59, b3, c3, d18), (a59,b3, c3, d19), (a59, b3, c3, d20), (a59, b3, c3, d21), (a59, b3, c3,d22), (a59, b4, c1, d1), (a59, b4, c1, d2), (a59, b4, c1, d3), (a59, b4,c1, d4), (a59, b4, c1, d5), (a59, b4, c1, d6), (a59, b4, c1, d7), (a59,b4, c1, d8), (a59, b4, c1, d9), (a59, b4, c1, d10), (a59, b4, c1, d11),(a59, b4, c1, d12), (a59, b4, c1, d13), (a59, b4, c1, d14), (a59, b4,c1, d15), (a59, b4, c1, d16), (a59, b4, c1, d17), (a59, b4, c1, d18),(a59, b4, c1, d19), (a59, b4, c1, d20), (a59, b4, c1, d21), (a59, b4,c1, d22), (a59, b4, c2, d1), (a59, b4, c2, d2), (a59, b4, c2, d3), (a59,b4, c2, d4), (a59, b4, c2, d5), (a59, b4, c2, d6), (a59, b4, c2, d7),(a59, b4, c2, d8), (a59, b4, c2, d9), (a59, b4, c2, d10), (a59, b4, c2,d11), (a59, b4, c2, d12), (a59, b4, c2, d13), (a59, b4, c2, d14), (a59,b4, c2, d15), (a59, b4, c2, d16), (a59, b4, c2, d17), (a59, b4, c2,d18), (a59, b4, c2, d19), (a59, b4, c2, d20), (a59, b4, c2, d21), (a59,b4, c2, d22), (a59, b4, c3, d1), (a59, b4, c3, d2), (a59, b4, c3, d3),(a59, b4, c3, d4), (a59, b4, c3, d5), (a59, b4, c3, d6), (a59, b4, c3,d7), (a59, b4, c3, d8), (a59, b4, c3, d9), (a59, b4, c3, d10), (a59, b4,c3, d11), (a59, b4, c3, d12), (a59, b4, c3, d13), (a59, b4, c3, d14),(a59, b4, c3, d15), (a59, b4, c3, d16), (a59, b4, c3, d17), (a59, b4,c3, d18), (a59, b4, c3, d19), (a59, b4, c3, d20), (a59, b4, c3, d21),(a59, b4, c3, d22), (a59, b5, c1, d1), (a59, b5, c1, d2), (a59, b5, c1,d3), (a59, b5, c1, d4), (a59, b5, c1, d5), (a59, b5, c1, d6), (a59, b5,c1, d7), (a59, b5, c1, d8), (a59, b5, c1, d9), (a59, b5, c1, d10), (a59,b5, c1, d11), (a59, b5, c1, d12), (a59, b5, c1, d13), (a59, b5, c1,d14), (a59, b5, c1, d15), (a59, b5, c1, d16), (a59, b5, c1, d17), (a59,b5, c1, d18), (a59, b5, c1, d19), (a59, b5, c1, d20), (a59, b5, c1,d21), (a59, b5, c1, d22), (a59, b5, c2, d1), (a59, b5, c2, d2), (a59,b5, c2, d3), (a59, b5, c2, d4), (a59, b5, c2, d15), (a59, b5, c2, d16),(a59, b5, c2, d7), (a59, b5, c2, d18), (a59, b5, c2, d9), (a59, b5, c2,d10), (a59, b5, c2, d11), (a59, b5, c2, d12), (a59, b5, c2, d13), (a59,b5, c2, d14), (a59, b5, c2, d15), (a59, b5, c2, d16), (a59, b5, c2,d17), (a59, b5, c2, d18), (a59, b5, c2, d19), (a59, b5, c2, d20), (a59,b5, c2, d21), (a59, b5, c2, d22), (a59, b5, c3, d1), (a59, b5, c3, d2),(a59, b5, c3, d3), (a59, b5, c3, d4), (a59, b5, c3, d5), (a59, b5, c3,d6), (a59, b5, c3, d7), (a59, b5, c3, d8), (a59, b5, c3, d9), (a59, b5,c3, d10), (a59, b5, c3, d11), (a59, b5, c3, d12), (a59, b5, c3, d13),(a59, b5, c3, d14), (a59, b5, c3, d15), (a59, b5, c3, d16), (a59, b5,c3, d17), (a59, b5, c3, d18), (a59, b5, c3, d19), (a59, b5, c3, d20),(a59, b5, c3, d21), (a59, b5, c3, d22), (a59, b6, c1, d11), (a59, b6,c1, d2), (a59, b6, c1, d3), (a59, b6, c1, d4), (a59, b6, c1, d5), (a59,b6, c1, d6), (a59, b6, c1, d7), (a59, b6, c1, d8), (a59, b6, c1, d9),(a59, b6, c1, d10), (a59, b6, c1, d11), (a59, b6, c1, d12), (a59, b6,c1, d13), (a59, b6, c1, d14), (a59, b6, c1, d15), (a59, b6, c1, d16),(a59, b6, c1, d17), (a59, b6, c1, d18), (a59, b6, c1, d19), (a59, b6,c1, d20), (a59, b6, c1, d21), (a59, b6, c1, d22), (a59, b6, c2, d1),(a59, b6, c2, d2), (a59, b6, c2, d3), (a59, b6, c2, d4), (a59, b6, c2,d5), (a59, b6, c2, d6), (a59, b6, c2, d7), (a59, b6, c2, d8), (a59, b6,c2, d9), (a59, b6, c2, d10), (a59, b6, c2, d11), (a59, b6, c2, d12),(a59, b6, c2, d13), (a59, b6, c2, d14), (a59, b6, c2, d15), (a59, b6,c2, d16), (a59, b6, c2, d17), (a59, b6, c2, d18), (a55, b6, c2, d19),(a59, b6, c2, d20), (a59, b6, c2, d21), (a59, b6, c2, d22), (a59, b6,c3, d1), (a59, b6, c3, d2), (a59, b6, c3, d3), (a59, b6, c3, d4), (a59,b6, c3, d5), (a59, b6, c3, d6), (a59, b6, c3, d7), (a59, b6, c3, d6),(a59, b6, c3, d9), (a59, b6, c3, d10), (a59, b6, c3, d11), (a59, b6, c3,d12), (a59, b6, c3, d13), (a59, b6, c3, d14), (a59, b6, c3, d15), (a59,b6, c3, d16), (a59, b6, c3, d17), (a59, b6, c3, d18), (a59, b6, c3,d19), (a59, b6, c3, d20), (a59, b6, c3, d21), (a59, b6, c3, d22), (a60,b1, c1, d1), (a60, b1, c1, d2), (a60, b1, c1, d3), (a60, b1, c1, d4),(a60, b1, c1, d5), (a60, b1, c1, d6), (a60, b1, c1, d7), (a60, b1, c1,d8), (a60, b1, c1, d9), (a60, b1, c1, d10), (a60, b1, c1, d11), (a60,b1, c1, d12), (a60, b1, c1, d13), (a60, b1, c1, d14), (a60, b1, c1,d15), (a60, b1, c1, d16), (a60, b1, c1, d17), (a60, b1, c1, d18), (a60,b1, c1, d19), (a60, b1, c1, d20), (a60, b1, c1, d21), (a60, b1, c1,d22), (a60, b1, c2, d1), (a60, b1, c2, d2), (a60, b1, c2, d3), (a60, b1,c2, d4), (a60, b1, c2, d5), (a60, b1, c2, d6), (a60, b1, c2, d7), (a60,b1, c2, d8), (a60, b1, c2, d9), (a60, b1, c2, d10), (a60, b1, c2, d11),(a60, b1, c2, d12), (a60, b1, c2, d13), (a60, b1, c2, d14), (a60, b1,c2, d15), (a60, b1, c2, d16), (a60, b1, c2, d17), (a60, b1, c2, d18),(a60, b1, c2, d19), (a60, b1, c2, d20), (a60, b1, c2, d21), (a60, b1,c2, d22), (a60, b1, c3, d1), (a60, b1, c3, d2), (a60, b1, c3, d3), (a60,b1, c3, d4), (a60, b1, c3, d5), (a60, b1, c3, d6), (a60, b1, c3, d7),(a60, b1, c3, d8), (a60, b1, c3, d9), (a60, b1, c3, d10), (a60, b1, c3,d11), (a60, b1, c3, d12), (a60, b1, c3, d13), (a60, b1, c3, d14), (a60,b1, c3, d15), (a60, b1, c3, d16), (a60, b1, c3, d17), (a60, b1, c3,d18), (a60, b1, c3, d19), (a60, b1, c3, d20), (a60, b1, c3, d21), (a60,b1, c3, d22), (a60, b2, c1, d1), (a60, b2, c1, d2), (a60, b2, c1, d3),(a60, b2, c1, d4), (a60, b2, c1, d5), (a60, b2, c1, d6), (a60, b2, c1,d7), (a60, b2, c1, d8), (a60, b2, c1, d9), (a60, b2, c1, d10), (a60, b2,c1, d11), (a60, b2, c1, d12), (a60, b2, c1, d13), (a60, b2, c1, d14),(a60, b2, c1, d15), (a60, b2, c1, d16), 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d2),(a60, b3, c1, d3), (a60, b5, c1, d4), (a60, b5, c1, d5), (a60, b3, c1,d6), (a60, b3, c1, d7), (a60, b3, c1, d8), (a60, b3, c1, d9), (a60, b3,c1, d10), (a60, b3, c1, d11), (a60, b3, c1, d12), (a60, b3, c1, d13),(a60, b3, c1, d14), (a60, b3, c1, d15), (a60, b3, c1, d16), (a60, b3,c1, d17), (a60, b5, c1, d18), (a60, b3, c3, d19), (a60, b3, c1, d20),(a60, b3, c1, d21), (a60, b3, c1, d22), (a60, b3, c2, d1), (a60, b3, c2,d2), (a60, b3, c2, d3), (a60, b3, c2, d4), (a60, b3, c2, d5), (a60, b3,c2, d6), (a60, b3, c2, d7), (a60, b3, c2, d8), (a60, b3, c2, d9), (a60,b3, c2, d10), (a60, b3, c2, d11), (a60, b3, c2, d12), (a60, b3, c2,d13), (a60, b3, c2, d14), (a60, b3, c2, d15), (a60, b3, c2, d16), (a60,b5, c2, d17), (a60, b3, c2, d18), (a60, b3, c2, d19), (a60, b3, c2,d20), (a60, b3, c2, d21), (a60, b3, c2, d22), (a60, b3, c3, d1), (a60,b3, c3, d2), (a60, b3, c3, d3) (a60, b3, c3, d4), (a60, b3, c3, d5),(a60, b3, c3, d6), (a60, b3, c3, d7), (a60, b3, c3, d8), (a60, b3, c3,d9), (a60, b3, c3, d10), (a60, b3, c3, d11), (a60, b3, c3, d12), (a60,b3, c3, d13), (a60, b3, c3, d14), (a60, b3, c3, d15), (a60, b3, c3,d16), (a60, b3, c3, d17), (a60, b3, c3, d18), (a60, b3, c3, d19), (a60,b3, c3, d20), (a60, b3, c3, d21), (a60, b3, c3, d22), (a60, b4, c1, d1),(a60, b4, c1, d2), (a60, b4, c1, d3), (a60, b4, c1, d4), (a60, b4, c1,d5), (a60, b4, c1, d6), (a60, b4, c1, d7), (a60, b4, c1, d5), (a60, b4,c1, d9), (a60, b4, c1, d10), (a60, b4, c1, d11), (a60, b4, c1, d12),(a60, b4, c1, d13), (a60, b4, c1, d14), (a60, b4, c1, d15), (a60, b4,c1, d16), (a60, b4, c1, d17), (a60, b4, c1, d18), (a60, b4, c1, d19),(a60, b4, c1, d20), (a60, b4, c1, d21), (a60, b4, c2, d22), (a60, b4,c2, d1), (a60, b4, c2, d2), (a60, b4, c2, d3), (a60, b4, c2, d4), (a60,b4, c2, d5), (a60, b4, c2, d6), (a60, b4, c2, d7), (a60, b4, c2, d8),(a60, b4, c2, d9), (a60, b4, c2, d10), (a60, b4, c2, d11), (a60, b4, c2,d12), (a60, b4, c2, d13), (a60, b4, c2, d14), (a60, b4, c2, d15), (a60,b4, c2, d16), (a60, b4, c2, d17), (a60, 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c1, d1), (a62, b2, c1, d2), (a62,b2, c1, d3), (a62, b2, c1, d6), (a62, b2, c1, d5), (a62, b2, c1, d6),(a62, b2, c1, d7), (a62, b2, c1, d8), (a62, b2, c1, d9), (a62, b2, c1,d10), (a62, b2, c1, d11), (a62, b2, c1, d12), (a62, b2, c1, d13), (a62,b2, c1, d14), (a62, b2, c1, d15), (a62, b2, c1, d16), (a62, b2, c1,d17), (a62, b2, c1, d18), (a62, b2, c1, d19), (a62, b2, c1, d20), (a62,b2, c1, d21), (a62, b2, c1, d22), (a62, b2, c2, d1), (a62, b2, c2, d2),(a62, b2, c2, d3), (a62, b2, c2, d4), (a62, b2, c2, d5), (a62, b2, c2,d6), (a62, b2, c2, d7), (a62, b2, c2, d8), (a62, b2, c2, d9), (a62, b2,c2, d10), (a62, b2, c2, d11), (a62, b2, c2, d12), (a62, b2, c2, d13),(a62, b2, c2, d14), (a62, b2, c2, d15), (a62, b2, c2, d16), (a62, b2,c2, d17), (a62, b2, c2, d18), (a62, b2, c2, d19), (a62, b2, c2, d20),(a62, b2, c2, d21), (a62, b2, c2, d22), (a62, b2, c3, d1), (a62, b2, c3,d2), (a62, b2, c3, d3), (a62, b2, c3, d4), (a62, b2, c3, d5), (a62, b2,c3, d6), (a62, b2, c3, d7), (a62, b2, c3, d8), (a62, b2, 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c1,d21), (a68, b5, c1, d22), (a68, b5, c2, d1), (a68, b5, c2, d2), (a68,b5, c2, d3), (a68, b5, c2, d4), (a68, b5, c2, d5), (a68, b5, c2, d6),(a68, b5, c2, d7), (a68, b5, c2, d8), (a68, b5, c2, d9), (a68, b5, c2,d10), (a68, b5, c2, d11), (a68, b5, c2, d12), (a68, b5, c2, d13), (a68,b5, c2, d14), (a68, b5, c2, d15), (a68, b5, c2, d16), (a68, b5, c2,d17), (a68, b5, c2, d18), (a68, b5, c2, d19), (a68, b5, c2, d20), (a68,b5, c2, d21), (a68, b5, c2, d22), (a68, b5, c3, d1), (a68, b5, c3, d2),(a38, b5, c3, d3), (a68, b5, c3, d4), (a38, b5, c3, d5), (a68, b5, c3,d5), (a55, b5, c3, d7), (a68, b5, c3, d8), (a68, b5, c3, d9), (a68, b5,c3, d10), (a68, b5, c3, d11), (a68, b5, c3, d12), (a55, b5, c3, d13),(a68, b5, c3, d14), (a55, b5, c3, d15), (a68, b5, c3, d16), (a68, b5,c3, d17), (a68, b5, c3, d18), (a68, b5, c3, d19), (a68, b5, c3, d20),(a55, b5, c3, d21), (a68, b5, c3, d22), (a68, b5, c1, d1), (a68, b5, c1,d2), (a55, b5, c1, d3), (a68, b5, c1, d4), (a68, b6, c1, d5), (a68, b5,c1, d6), (a68, b6, c1, d7), (a68, b6, c1, d8), (a68, b6, c1, d9), (a68,b6, c1, d10), (a68, b6, c1, d11), (a68, b6, c1, d12), (a68, b6, c1,d13), (a68, b6, c1, d14), (a68, b6, c1, d15), (a68, b6, c1, d16), (a68,b6, c1, d17), (a68, b6, c1, d18), (a68, b6, c1, d19), (a68, b6, c1,d20), (a68, b6, c1, d21), (a68, b6, c1, d22), (a68, b6, c2, d1), (a68,b6, c2, d2), (a68, b6, c2, d3), (a68, b6, c2, d4), (a68, b6, c2, d5),(a68, b6, c2, d6), (a68, b6, c2, d7), (a68, b6, c2, d8), (a68, b6, c2,d9), (a68, b6, c2, d10), (a68, b6, c2, d11), (a68, b6, c2, d12), (a68,b6, c2, d13), (a68, b6, c2, d14), (a68, b6, c2, d15), (a68, b6, c2,d16), (a68, b6, c2, d17), (a68, b6, c2, d18), (a68, b6, c2, d19), (a68,b6, c2, d20), (a68, b6, c2, d21), (a68, b6, c2, d22), (a68, b6, c3, d1),(a68, b6, c3, d2), (a68, b6, c3, d3), (a68, b6, c3, d4), (a68, b6, c3,d5), (a68, b6, c3, d6), (a68, b6, c3, d7), (a68, b6, c3, d8), (a68, b6,c3, d9), (a68, b6, c3, d10), (a68, b6, c3, d11), (a68, b6, c3, d12),(a68, b6, c3, d13), (a68, b6, c3, d14), (a68, b6, c3, d15), (a68, b6,c3, d16), (a68, b6, c3, d17), (a68, b6, c3, d18), (a68, b6, c3, d19),(a68, b6, c3, d20), (a68, b6, c3, d21), (a68, b6, c3, d22), (a69, b1,c1, d1), (a69, b1, c1, d2), (a69, b1, c1, d3), (a69, b1, c1, d4), (a69,b1, c1, d5), (a69, b1, c1, d6), (a69, b1, c1, d7), (a69, b1, c1, d8),(a69, b1, c1, d9), (a69, b1, c1, d10), (a69, b1, c1, d11), (a69, b1, c1,d12), (a69, b1, c1, d13), (a69, b1, c1, d14), (a69, b1, c1, d15), (a69,b1, c1, d10), (a69, b1, c1, d17), (a69, b1, c1, d18), (a69, b1, c1,d19), (a69, b1, c1, d20), (a69, b1, c1, d21), (a69, b1, c1, d22), (a69,b1, c2, d1), (a69, b1, c2, d2), (a69, b1, c2, d3), (a69, b1, c2, d4),(a69, b1, c2, d5), (a69, b1, c2, d6), (a69, b1, c2, d7), (a66, b1, c2,d8), (a69, b1, c2, d9), (a69, b1, c2, d10), (a69, b1, c2, d11), (a69,b1, c2, d12), (a69, b1, c2, d13), (a69, b1, c2, d14), (a69, b1, c2,d15), (a66, b1, c2, d16), (a69, b1, c2, d17), (a69, b1, c2, d18), (a69,b1, c2, d19), (a59, b1, c2, d20), (a69, b1, c2, d21), (a69, b1, c2,d22), (a69, b1, c3, d1), (a69, b1, c3, d2), (a69, b1, c3, d3), (a69, b1,c3, d4), (a69, b1, c3, d5), (a69, b1, c3, d6), (a69, b1, c3, d7), (a69,b1, c3, d8), (a69, b1, c3, d9), (a69, b1, c3, d10), (a69, b1, c3, d11),(a69, b1, c3, d12), (a69, b1, c3, d13), (a69, b1, c3, d14), (a69, b1,c3, d15), (a69, b1, c3, d16), (a69, b1, c3, d17), (a69, b1, c3, d18),(a69, b1, c3, d19), (a69, b1, c3, d20), (a69, b1, c3, d21), (a69, b1,c3, d22), (a69, b2, c1, d1), (a69, b2, c1, d2), (a69, b2, c1, d3), (a69,b2, c1, d4), (a69, b2, c1, d5), (a69, b2, c1, d6), (a69, b2, c1, d7),(a69, b2, c1, d8), (a69, b2, c1, d19), (a69, b2, c1, d10), (a69, b2, c1,d11), (a69, b2, c1, d12), (a69, b2, c1, d13), (a69, b2, c1, d14), (a69,b2, c1, d15), (a69, b2, c1, d16), (a69, b2, c1, d17), (a69, b2, c1,d18), (a9, b2, c1, d19), (a69, b2, c1, d20), (a69, b2, c1, d21), (a69,b2, c1, d22), (a69, b2, c2, d1), (a69, b2, c2, d2), (a69, b2, c2, d3),(a69, b2, c2, d4), (a69, b2, c2, d5), (a69, b2, c2, d6), (a69, b2, c2,d7), (a69, b2, c2, d8), (a69, b2, c2, d9), (a69, b2, c2, d10), (a69, b2,c2, d11), (a69, b2, c2, d12), (a69, b2, c2, d13), (a69, b2, c2, d14),(a69, b2, c2, d15), (a69, b2, c2, d16), (a69, b2, c2, d17), (a69, b2,c2, d18), (a69, b2, c2, d10), (a69, b2, c2, d20), (a69, b2, c2, d21),(a66, b2, c2, d22), (a69, b2, c3, d1), (a69, b2, c3, d2), (a69, b2, c3,d3), (a69, b2, c3, d4), (a66, b2, c3, d5), (a69, b2, c3, d6), (a69, b2,c3, d7), (a69, b2, c3, d8), (a69, b2, c3, d9), (a69, b2, c3, d10), (a69,b2, c3, d11), (a69, b2, c3, d12), (a69, b2, c3, d13), (a69, b2, c3,d14), (a69, b2, c3, d15), (a69, b2, c3, d16), (a69, b2, c3, d17), (a69,b2, c3, d18), (a66, b2, c3, d19), (a69, b2, c3, d20), (a69, b2, c3,d21), (a69, b2, c3, d22), (a69, b2, c3, d1), (a69, b2, c3, d2), (a69,b3, c1, d3), (a69, b3, c1, d4), (a69, b3, c1, d5), (a69, b3, c1, d6),(a69, b3, c1, d7), (a69, b3, c1, d8), (a69, b3, c1, d9), (a69, b3, c1,d10), (a69, b3, c1, d11), (a69, b3, c1, d12), (a69, b3, c1, d13), (a69,b3, c1, d14), (a69, b3, c1, d15), (a69, b3, c1, d16), (a69, b3, c1,d17), (a69, b3, c1, d18), (a66, b3, c1, d19), (a69, b3, c1, d20), (a69,b3, c1, d21), (a69, b3, c1, d22), (a69, b3, c2, d1), (a66, b3, c2, d2),(a69, b3, c2, d3), (a69, b3, c2, d4), (a69, b3, c2, d5), (a66, b3, c2,d6), (a69, b3, c2, d7), (a69, b3, c2, d8), (a69, b3, c2, d9), (a69, b3,c2, d10), (a69, b3, c2, d11), (a69, b3, c2, d12), (a69, b3, c2, d13),(a69, b3, c2, d14), (a69, b3, c2, d15), (a69, b3, c2, d16), (a69, b3,c2, d17), (a69, b3, c2, d18), (a69, b3, c2, d19), (a69, b3, c2, d20),(a69, b3, c2, d21), (a69, b3, c2, d22), (a69, b3, c3, d1), (a69, b3, c3,d2), (a69, b3, c3, d3), (a69, b3, c3, d4), (a69, b3, c3, d5), (a69, b3,c3, d6), (a69, b3, c3, d7), (a69, b3, c3, d3), (a69, b3, c3, d9), (a69,b3, c3, d10), (a69, b3, c3, d11), (a69, b3, c3, d12), (a69, b3, c3,d13), (a69, b3, c3, d14), (a69, b3, c3, d15), (a69, b3, c3, d16), (a69,b3, c3, d17), (a69, b3, c3, d18), (a69, b5, c3, d19), (a69, b3, c3,d20), (a69, b3, c3, d21), (a69, b3, c3, d22), (a69, b4, c1, d1), (a69,b4, c1, d2), (a69, b4, c1, d3), (a69, b4, c1, d4), (a69, b4, c1, d5),(a69, b4, c1, d6), (a69, b4, c1, d7), (a69, b4, c1, d8), (a69, b4, c1,d9), (a69, b4, c1, d10), (a69, b4, c1, d11), (a69, b4, c1, d12), (a69,b4, c1, d13), (a69, b4, c1, d14), (a69, b4, c1, d15), (a69, b4, c1,d16), (a69, b4, c1, d17), (a69, b4, c1, d18), (a69, b4, c1, d19), (a69,b4, c1, d20), (a69, b4, c1, d21), (a69, b4, c1, d22), (a69, b4, c2, d1),(a69, b4, c2, d2), (a69, b4, c2, d3), (a69, b4, c2, d4), (a69, b4, c2,d5), (a69, b4, c2, d6), (a66, b4, c2, d7), (a69, b4, c2, d3), (a69, b4,c2, d9), (a69, b4, c2, d10), (a69, b4, c2, d11), (a69, b4, c2, d12),(a69, b4, c2, d13), (a69, b4, c2, d14), (a69, b4, c2, d15), (a69, b4,c2, d16), (a69, b4, c2, d17), (a69, b4, c2, d13), (a69, b4, c2, d14),(a69, b4, c2, d20), (a66, b4, c2, d21), (a69, b4, c2, d22), (a69, b4,c3, d1), (a69, b4, c3, d2), (a69, b4, c3, d3), (a69, b4, c3, d4), (a66,b4, c3, d5), (a69, b4, c3, d6), (a69, b4, c3, d7), (a69, b4, c3, d8,(a69, b4, c3, d9), (a69, b4, c3, d10), (a69, b4, c3, d11), (a69, b4, c3,d12), (a69, b4, c3, d13), (a69, b4, c3, d14), (a69, b4, c3, d15), (a69,b4, c3, d16), (a69, b4, c3, d17), (a69, b4, c3, d18), (a69, b4, c3,d19), (a66, b4, c3, d20), (a69, b4, c3, d21), (a69, b4, c3, d22), (a69,b5, c1, d1), (a69, b5, c1, d2), (a69, b5, c1, d3), (a69, b5, c1, d4),(a69, b5, c1, d5), (a39, b5, c1, d6), (a69, b5, c1, d7), (a69, b5, c1,d8), (a69, b5, c1, d9), (a69, b5, c1, d10), (a69, b5, c1, d11), (a69,b5, c1, d12), (a69, b5, c1, d13), (a69, b5, c1, d14), (a69, b5, c1,d15), (a69, b5, c1, d16), (a69, b5, c1, d17), (a69, b5, c1, d18), (a69,b5, c1, d19), (a69, b5, c1, d20), (a69, b5, c1, d21), (a69, b5, c1,d22), (a69, b5, c2, d1), (a69, b5, c2, d2), (a69, b5, c2, d3), (a69, b5,c2, d4), (a69, b5, c2, d5), (a69, b5, c2, d6), (a69, b5, c2, d7), (a69,b5, c2, d8), (a69, b5, c2, d9), (a69, b5, c2, d10), (a69, b5, c2, d11),(a69, b5, c2, d12), (a69, b5, c2, d13), (a69, b5, c2, d14), (a69, b5,c2, d15), (a69, b5, c2, d16), (a69, b5, c2, d17), (a69, b5, c2, d18),(a69, b5, c2, d19), (a69, b5, c2, d20), (a69, b5, c2, d21), (a69, b5,c2, d22), (a69, b5, c3, d1), (a69, b5, c3, d2), (a69, b5, c3, d3), (a69,b5, c3, d4), (a69, b5, c3, d5), (a69, b5, c3, d6), (a69, b5, c3, d7),(a69, b5, c3, d8), (a69, b5, c3, d9), (a69, b5, c3, d10), (a69, b5, c3,d11), (a69, b5, c3, d12), (a69, b5, c3, d13), (a69, b5, c3, d14), (a69,b5, c3, d15), (a69, b5, c3, d16), (a69, b5, c3, d17), (a69, b5, c3,d18), (a69, b5, c3, d19), (a69, b5, c3, d20), (a69, b5, c3, d21), (a69,b5, c3, d22), (a69, b6, c1, d1), (a69, b6, c1, d2), (a69, b6, c1, d3),(a69, b6, c1, d4), (a69, b6, c1, d5), (a69, b6, c1, d6), (a69, b6, c1,d7), (a69, b6, c1, d8), (a69, b6, c1, d9), (a69, b6, c1, d10), (a69, b6,c1, d11), (a69, b6, c1, d12), (a69, b6, c1, d13), (a69, b6, c1, d14),(a69, b6, c1, d15), (a69, b6, c1, d16), (a69, b6, c1, d17), (a69, b6,c1, d18), (a69, b6, c1, d19), (a69, b6, c1, d20), (a69, b6, c1, d21),(a69, b6, c1, d22), (a69, b6, c2, d1), (a69, b6, c2, d2), (a69, b6, c2,d3), (a69, b6, c2, d4), (a69, b6, c2, d5), (a69, b6, c2, d6), (a69, b6,c2, d7), (a69, b6, c2, d8), (a69, b6, c2, d9), (a69, b6, c2, d10), (a69,b6, c2, d11), (a69, b6, c2, d12), (a69, b6, c2, d13), (a69, b6, c2,d14), (a69, b6, c2, d15), (a69, b6, c2, d16), (a69, b6, c2, d17), (a69,b6, c2, d18), (a69, b6, c2, d19), (a69, b6, c2, d20), (a69, b6, c2,d21), (a69, b6, c2, d22), (a69, b6, c3, d1), (a69, b6, c3, d2), (a69,b6, c3, d3), (a69, b6, c3, d4), (a69, b6, c3, d5), (a69, b6, c3, d6),(a69, b6, c3, d7), (a69, b6, c3, d8), (a69, b6, c3, d9), (a69, b6, c3,d10), (a69, b6, c3, d11), (a69, b6, c3, d12), (a69, b6, c3, d13), (a69,b6, c3, d14), (a69, b6, c3, d15), (a69, b6, c3, d16), (a69, b6, c3,d17), (a69, b6, c3, d18), (a69, b6, c3, d19), (a69, b6, c3, d20), (a69,b6, c3, d21), (a69, b6, c3, d22), (a70, b1, c1, d1), (a70, b1, c1, d2),(a70, b1, c1, d3), (a70, b1, c1, d4), (a70, b1, c1, d5), (a70, b1, c1,d6), (a70, b1, c1, d7), (a70, b1, c1, d8), (a70, b1, c1, d9), (a70, b1,c1, d10), (a70, b1, c1, d11), (a70, b1, c1, d12), (a70, b1, c1, d13),(a70, b1, c1, d14), (a70, b1, c1, d15), (a70, b1, c1, d16), (a70, b1,c1, d17), (a70, b1, c1, d18), (a70, b1, c1, d19), (a70, b1, c1, d20),(a70, b1, c1, d21), (a70, b1, c1, d22), (a70, b1, c2, d1), (a70, b1, c2,d2), (a70, b1, c2, d3), (a70, b1, c2, d4), (a70, b1, c2, d5), (a70, b1,c2, d6), (a70, b1, c2, d7), (a70, b1, c2, d8), (a70, b1, c2, d9), (a70,b1, c2, d10), (a70, b1, c2, d11), (a70, b1, c2, d12), (a70, b1, c2,d13), (a70, b1, c2, d14), (a70, b1, c2, d15), (a70, b1, c2, d16), (a70,b1, c2, d17), (a70, b1, c2, d18), (a70, b1, c2, d19), (a70, b1, c2,d20), (a70, b1, c2, d21), (a70, b1, c2, d22), (a70, b1, c3, d1), (a70,b1, c3, d2), (a70, b1, c3, d3), (a70, b1, c3, d4), (a70, b1, c3, d5),(a70, b1, c3, d6), (a70, b1, c3, d7), (a70, b1, c3, d8), (a70, b1, c3,d9), (a70, b1, c3, d10), (a70, b1, c3, d11), (a70, b1, c3, d12), (a70,b1, c3, d13), (a70, b1, c3, d14), (a70, b1, c3, d15), (a70, b1, c3,d16), (a70, b1, c3, d17), (a70, b1, c3, d18), (a70, b1, c3, d19), (a70,b1, c3, d20), (a70, b1, c3, d21), (a70, b1, c3, d22), (a70, b2, c1, d1),(a70, b2, c1, d2), (a70, b2, c1, d3), (a70, b2, c1, d4), (a70, b2, c1,d5), (a70, b2, c1, d6), (a70, b2, c1, d7), (a70, b2, c1, d8), (a70, b2,c1, d9), (a70, b2, c1, d10), (a70, b2, c1, d11), (a70, b2, c1, d12),(a70, b2, c1, d13), (a70, b2, c1, d14), (a70, b2, c1, d15), (a70, b2,c1, d16), (a70, b2, c1, d17), (a70, b2, c1, d18), (a70, b2, c1, d19),(a70, b2, c1, d20), (a70, b2, c1, d21), (a70, b2, c1, d22), (a70, b2,c2, d1), (a70, b2, c2, d2), (a70, b2, c2, d3), (a70, b2, c2, d4), (a70,b2, c2, d5), (a70, b2, c2, d6), (a70, b2, c2, d7), (a70, b2, c2, d8),(a70, b2, c2, d9), (a70, b2, c2, d10), (a70, b2, c2, d11), (a70, b2, c2,d12), (a70, b2, c2, d13), (a70, b2, c2, d14), (a70, b2, c2, d15), (a70,b2, c2, d16), (a70, b2, c2, d17), (a70, b2, c2, d18), (a70, b2, c2,d19), (a70, b2, c2, d20), (a70, b2, c2, d21), (a70, b2, c2, d22), (a70,b2, c3, d1), (a70, b2, c3, d2), (a70, b2, c3, d3), (a70, b2, c3, d4),(a70, b2, c3, d5), (a70, b2, c3, d6), (a70, b2, c3, d7), (a70, b2, c3,d8), (a70, b2, c3, d9), (a70, b2, c3, d10), (a70, b2, c3, d11), (a70,b2, c3, d12), (a70, b2, c3, d13), (a70, b2, c3, d14), (a70, b2, c3,d15), (a70, b2, c3, d16), (a70, b2, c3, d17), (a70, b2, c3, d18), (a70,b2, c3, d19), (a70, b2, c3, d20), (a70, b2, c3, d21), (a70, b2, c3,d22), (a70, b3, c1, d1), (a70, b3, c1, d2), (a70, b3, c1, d3), (a70, b3,c1, d4), (a70, b3, c1, d5), (a70, b3, c1, d6), (a70, b3, c1, d7), (a70,b3, c1, d8), (a70, b3, c1, d9), (a70, b3, c1, d10), (a70, b3, c1, d11),(a70, b3, c1, d12), (a70, b3, c1, d13), (a70, b3, c1, d14), (a70, b3,c1, d15), (a70, b3, c1, d16), (a70, b3, c1, d17), (a70, b3, c1, d18),(a70, b3, c1, d19), (a70, b3, c1, d20), (a70, b3, c1, d21), (a70, b3,c1, d22), (a70, b3, c2, d1), (a70, b3, c2, d2), (a70, b3, c2, d3), (a70,b3, c2, d4), (a70, b3, c2, d5), (a70, b3, c2, d6), (a70, b3, c2, d7),(a70, b3, c2, d8), (a70, b3, c2, d9), (a70, b3, c2, d10), (a70, b3, c2,d11), (a70, b3, c2, d12), (a70, b3, c2, d13), (a70, b3, c2, d14), (a70,b3, c2, d15), (a70, b3, c2, d16), (a70, b3, c2, d17), (a70, b3, c2,d18), (a70, b3, c2, d19), (a70, b3, c2, d20), (a70, b3, c2, d21), (a70,b3, c2, d22), (a70, b3, c3, d1), (a70, b3, c3, d2), (a70, b3, c3, d3),(a70, b3, c3, d4), (a70, b3, c3, d5), (a70, b3, c3, d6), (a70, b3, c3,d7), (a70, b3, c3, d8), (a70, b3, c3, d9), (a70, b3, c3, d10), (a70, b3,c3, d11), (a70, b3, c3, d12), (a70, b3, c3, d13), (a70, b3, c3, d14),(a70, b3, c3, d15), (a70, b3, c3, d16), (a70, b3, c3, d17), (a70, b3,c3, d18), (a70, b3, c3, d19), (a70, b3, c3, d20), (a70, b3, c3, d21),(a70, b3, c3, d22), (a70, b4, c1, d1), (a70, b4, c1, d12), (a70, b4, c1,d13), (a70, b4, c1, d4), (a70, b4, c1, d5), (a70, b4, c1, d6), (a70, b4,c1, d7), (a70, b4, c1, d8), (a70, b4, c1, d9), (a70, b4, c1, d10), (a70,b4, c1, d11), (a70, b4, c1, d12), (a70, b4, c1, d13), (a70, b4, c1,d14), (a70, b4, c1, d15), (a70, b4, c1, d16), (a70, b4, c1, d17), (a70,b4, c1, d18), (a70, b4, c1, d19), (a70, b4, c1, d20), (a70, b4, c1,d21), (a70, b4, c1, d22), (a70, b4, c2, d1), (a70, b4, c2, d2), (a70,b4, c2, d3), (a70, b4, c2, d4), (a70, b4, c2, d5), (a70, b4, c2, d3),(a70, b4, c2, d7), (a70, b4, c2, d8), (a70, b4, c2, d9), (a70, b4, c2,d10), (a70, b4, c2, d11), (a70, b4, c2, d12), (a70, b4, c2, d13), (a70,b4, c2, d14), (a70, b4, c2, d15), (a70, b4, c2, d16), (a70, b4, c2,d17), (a70, b4, c2, d18), (a70, b4, c2, d19), (a70, b4, c2, d20), (a70,b4, c2, d21), (a70, b4, c2, d22), (a70, b4, c3, d1), (a70, b4, c3, d2),(a70, b4, c3, d3), (a70, b4, c3, d4), (a70, b4, c3, d5), (a70, b4, c3,d6), (a70, b4, c3, d7), (a70, b4, c3, d8), (a70, b4, c3, d9), (a70, b4,c3, d10), (a70, b4, c3, d11), (a70, b4, c3, d1), (a70, b4, c3, d13),(a70, b4, c3, d14), (a70, b4, c3, d15), (a70, b4, c3, d16), (a70, b4,c3, d17), (a70, b4, c3, d18), (a70, b4, c3, d19), (a70, b4, c3, d20),(a70, b4, c3, d21), (a70, b4, c3, d22), (a70, b5, c1, d1), (a70, b5, c1,d2), (a70, b5, c1, d3), (a70, b5, c1, d4), (a70, b5, c1, d5), (a70, b5,c1, d6), (a70, b5, c1, d7), (a70, b5, c1, d8), (a70, b5, c1, d9), (a70,b5, c1, d10), (a70, b5, c1, d11), (a70, b5, c1, d12), (a70, b5, c1,d13), (a70, b5, c1, d14), (a70, b5, c1, d15), (a70, b5, c1, d16), (a70,b5, c1, d17), (a70, b5, c1, d18), (a70, b5, c1, d19), (a70, b5, c1,d20), (a70, b5, c1, d21), (a70, b5, c1, d22), (a70, b5, c2, d1), (a70,b5, c2, d2), (a70, b5, c2, d3), (a70, b5, c2, d4), (a70, b5, c2, d5),(a70, b5, c2, d6), (a70, b5, c2, d7), (a70, b5, c2, d8), (a70, b5, c2,d9), (a70, b5, c2, d10), (a70, b5, c2, d11), (a70, b5, c2, d12), (a70,b5, c2, d13), (a70, b5, c2, d14), (a70, b5, c2, d15), (a70, b5, c2,d16), (a70, b5, c2, d17), (a70, b5, c2, d18), (a70, b5, c2, d19), (a70,b5, c2, d20), (a70, b5, c2, d21), (a70, b5, c2, d22), (a70, b5, c3, d1),(a70, b5, c3, d2), (a70, b5, c3, d3), (a70, b5, c3, d4), (a70, b5, c3,d5), (a70, b5, c3, d6), (a70, b5, c3, d7), (a70, b5, c3, d8), (a70, b5,c3, d9), (a70, b5, c3, d10), (a70, b5, c3, d11), (a70, b5, c3, d12),(a70, b5, c3, d13), (a70, b5, c3, d14), (a70, b5, c3, d15), (a70, b5,c3, d16), (a70, b5, c3, d17), (a10, b5, c3, d18), (a70, b5, c3, d19),(a70, b5, c3, d20), (a70, b5, c3, d21), (a70, b5, c3, d22), (a70, b5,c1, d1), (a70, b6, c1, d2), (a70, b6, c1, d3), (a70, b6, c1, d4), (a70,b6, c1, d5), (a70, b6, c1, d6), (a70, b6, c1, d7), (a70, b6, c1, d8),(a70, b6, c1, d9), (a70, b6, c1, d10), (a70, b6, c1, d11), (a70, b6, c1,d12), (a70, b6, c1, d13), (a70, b6, c1, d14), (a70, b6, c1, d15), (a70,b6, c1, d16), (a70, b6, c1, d17), (a70, b6, c1, d18), (a7, b2, c1, d19),(a70, b6, c1, d20), (a70, b6, c1, d21), (a70, b6, c1, d22), (a70, b6,c2, d1), (a70, b6, c2, d2), (a70, b6, c2, d3), (a70, b6, c2, d4), (a70,b6, c2, d5), (a70, b6, c2, d6), (a70, b6, c2, d7, (a70, b6, c2, d8),(a70, b6, c2, d9), (a70, b6, c2, d10), (a70, b6, c2, d11), (a70, b6, c2,d12), (a70, b6, c2, d13), (a70, b6, c2, d14), (a70, b6, c2, d15), (a70,b6, c2, d16), (a70, b6, c2, d17), (a70, b6, c2, d18), (a70, b6, c2,d19), (a70, b6, c2, d20), (a70, b6, c2, d21), (a70, b6, c2, d22), (a70,b6, c3, d1), (a70, b6, c3, d2), (a70, b6, c3, d3), (a70, b6, c3, d4),(a70, b6, c3, d5), (a70, b6, c3, d6), (a70, b6, c3, d7), (a70, b6, c3,d8), (a70, b6, c3, d9), (a70, b6, c3, d10), (a70, b6, c3, d11), (a70,b6, c3, d12), (a70, b6, c3, d13), (a70, c3, d14), (a70, b6, c3, d15),(a70, b6, c3, d16), (a70, b6, c3, d17), (a70, b6, c3, d18), (a70, b6,c3, d19), (a70, b6, c3, d20), (a70, b6, c3, d21), (a70, b6, c3, d22),(a71, b1, c1, d1), (a71, b1, c1, d2), (a71, b1, c1, d3), (a71, b1, c1,d4), (a71, b1, c1, d5), (a71, b1, c1, d6), (a71, b1, c1, d7), (a71, b1,c1, d8), (a71, b1, c1, d9), (a71, b1, c1, d10), (a71, b1, c1, d11),(a71, b1, c1, d12), (a71, b1, c1, d13), (a71, b1, c1, d14), (a71, b1,c1, d15), (a17, b1, c1, d16), (a71, b1, c1, d17), (a7, b1, c1, d18),(a71, b1, c1, d19), (a1, b1, c1, d20), (a1, b1, c1, d21), (a71, b1, c1,d22), (a71, b1, c2, d1), (a71, b1, c2, d2), (a71, b1, c2, d3), (a71, b1,c2, d4), (a1, b1, c2, d5), (a71, b1, c2, d6), (a71, b1, c2, d7), (a71,b1, c2, d8), (a71, b1, c2, d9), (a71, b1, c2, d10), (a71, b1, c2, d11),(a71, b1, c2, d12), (a71, b1, c2, d13), (a71, b1, c2, d14), (a71, b1,c2, d15), (a71, b1, c2, d16), (a71, b1, c2, d17), (a71, b1, c2, d18),(a71, b1, c2, d19), (a71, b1, c2, d20), (a71, b1, c2, d21), (a71, b1,c2, d22), (a71, b1, c3, d1), (a71, b1, c3, d2), (a71, b1, c3, d3), (a71,b1, c3, d4), (a71, b1, c3, d5), (a71, b1, c3, d6), (a71, b1, c3, d7),(a71, b1, c3, d8), (a71, b1, c3, d9), (a71, b1, c3, d10), (a71, b1, c3,d11), (a71, b1, c3, d12), (a71, b1, c3, d13), (a71, b1, c3, d14), (a71,b1, c3, d15), (a71, b1, c3, d16), (a71, b1, c3, d17), (a71, b1, c3,d18), (a71, b1, c3, d19), (a71, b1, c3, d20), (a71, b1, c3, d21), (a71,b1, c3, d22), (a71, b2, c1, d1), (a71, b2, c1, d2), (a71, b2, c1, d3),(a71, b2, c1, d4), (a71, b2, c1, d5), (a71, b2, c1, d6), (a71, b2, c1,d7), (a71, b2, c1, d8), (a71, b2, c1, d9), (a71, b2, c1, d10), (a71, b2,c1, d11), (a71, b2, c1, d12), (a71, b2, c1, d13), (a71, b2, c1, d14),(a71, b2, c1, d15) (a71, b2, c1, d16), (a71, b2, c1, d17), (a71, b2, c1,d18), (a71, b2, c1, d19), (a71, b2, c1, d20), (a71, b2, c1, d21), (a71,b2, c1, d22), (a71, b2, c2, d1), (a71, b2, c2, d2), (a71, b2, c2, d3),(a71, b2, c2, d4), (a71, b2, c2, d5), (a71, b2, c2, d6), (a71, b2, c2,d7), (a71, b2, c2, d8), (a71, b2, c2, d9), (a71, b2, c2, d10), (a71, b2,c2, d11), (a71, b2, c2, d12), (a71, b2, c2, d13), (a71, b2, c2, d14),(a71, b2, c2, d15), (a71, b2, c2, d16), (a71, b2, c2, d17), (a71, b2,c2, d18), (a71, b2, c2, d19), (a71, b2, c2, d20), (a71, b2, c2, d21),(a71, b2, c2, d22), (a71, b2, c3, d1), (a71, b2, c3, d2), (a71, b2, c3,d3), (a71, b2, c3, d4), (a71, b2, c3, d5), (a71, b2, c3, d6), (a71, b2,c3, d7), (a71, b2, c3, d8), (a71, b2, c3, d9), (a71, b2, c3, d10), (a71,b2, c3, d11), (a71, b2, c3, d2), (a71, b2, c3, d13), (a71, b2, c3, d14),(a71, b2, c3, d15), (a71, b2, c3, d16), (a71, b2, c3, d17), (a71, b2,c3, d18), (a71, b2, c3, d19), (a71, b2, c3, d20), (a7, b2, c3, d21),(a71, b2, c3, d22), (a71, b3, c1, d1), (a71, b3, c1, d2), (a71, b3, c1,d3), (a71, b3, c1, d4), (a71, b3, c1, d5), (a71, b3, c1, d6), (a71, b3,c1, d7), (a71, b3, c1, d8), (a71, b3, c1, d9), (a71, b3, c1, d10), (a71,b3, c1, d11), (a71, b3, c1, d12), (a71, b3, c1, d13), (a71, b3, c1,d14), (a71, b3, c1, d15), (a71, b3, c1, d16), (a71, b3, c1, d17), (a71,b3, c1, d18), (a71, b3, c1, d19), (a71, b3, c1, d20), (a71, b3, c1,d21), (a71, b3, c1, d22), (a71, b3, c2, d1), (a71, b3, c2, d2), (a71,b3, c2, d3), (a71, b3, c2, d4), (a71, b3, c2, d5), (a71, b3, c2, d6),(a71, b3, c2, d7), (a71, b3, c2, d8), (a71, b3, c2, d19), (a71, b3, c2,d10), (a71, b3, c2, d11), (a71, b3, c2, d12), (a71, b3, c2, d13), (a71,b3, c2, d14), (a71, b3, c2, d15), (a71, b3, c2, d16), (a71, b3, c2,d17), (a71, b3, c2, d18), (a71, b3, c2, d19), (a71, b3, c2, d20), (a71,b3, c2, d21), (a71, b3, c2, d22), (a71, b3, c3, d1), (a71, b3, c3, d2),(a71, b3, c3, d3), (a71, b3, c3, d4), (a71, b3, d5), (a71, b3, c3, d6),(a71, b3, c3, d7), (a71, b3, 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b1, c3, d3), (a72, b1, c3, d4), (a72, b1, c3, d5), (a72, b1, c3,d6), (a72, b1, c3, d7), (a72, b1, c3, d8), (a72, b1, c3, d9), (a72, b1,c3, d10), (a72, b1, c3, d11), (a72, b1, c3, d12), (a72, b1, c3, d13),(a72, b1, c3, d14), (a72, b1, c3, d15), (a72, b1, c3, d16), (a72, b1,c3, d17), (a72, b1, c3, d18), (a72, b1, c3, d19), (a72, b1, c3, d20),(a72, b1, c3, d21), (a72, b1, c3, d22), (a72, b2, c1, d1), (a72, b2, c1,d2), (a72, b2, c1, d3), (a72, b2, c1, d4), (a72, b2, c1, d5), (a72, b2,c1, d6), (a72, b2, c1, d7), (a72, b2, c1, d8), (a72, b2, c1, d9), (a72,b2, c1, d10), (a72, b2, c1, d11), (a72, b2, c1, d12), (a72, b2, c1,d13), (a72, b2, c1, d14), (a72, b2, c1, d15), (a72, b2, c1, d16), (a72,b2, c1, d17), (a72, b2, c1, d18), (a72, b2, c1, d19), (a72, b2, c1,d20), (a72, b2, c1, d21), (a72, b2, c1, d22), (a72, b2, c2, d1), (a72,b2, c2, d2), (a72, b2, c2, d3), (a72, b2, c2, d4), (a72, b2, c2, d5),(a72, b2, c2, d6), (a72, b2, c2, d7), (a72, b2, c2, d8), (a72, b2, c2,d9), (a72, b2, c2, d10), (a72, 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(a76, b4,c2, d9), (a76, b4, c2, d10), (a76, b4, c2, d11), (a76, b4, c2, d12),(a76, b4, c2, d13), (a76, b4, c2, d14), (a76, b4, c2, d15), (a76, b4,c2, d16), (a76, b4, c2, d17), (a76, b4, c2, d18), (a76, b4, c2, d19),(a76, b4, c2, d20), (a76, b4, c2, d21), (a76, b4, c2, d22), (a76, b4,c3, d1), (a76, b4, c3, d2), (a76, b4, c3, d3), (a76, b4, c3, d4), (a76,b4, c3, d5), (a76, b4, c3, d6), (a76, b4, c3, d7), (a76, b4, c3, d8),(a76, b4, c3, d9), (a76, b4, c3, d10), (a76, b4, c3, d11), (a76, b4, c3,d12), (a76, b4, c3, d13), (a76, b4, c3, d14), (a76, b4, c3, d15), (a76,b4, c3, d16), (a76, b4, c3, d17), (a76, b4, c3, d18), (a76, b4, c3,d19), (a76, b4, c3, d20), (a76, b4, c3, d21), (a76, b4, c3, d22), (a76,b5, c1, d1), (a76, b5, c1, d2), (a76, b5, c1, d3), (a76, b5, c1, d4),(a76, b5, c1, d5), (a76, b5, c1, d6), (a76, b5, c1, d7), (a76, b5, c1,d8), (a76, b5, c1, d9), (a76, b5, c1, d10), (a76, b5, c1, d11), (a76,b5, c1, d12), (a76, b5, c1, d13), (a76, b5, c1, d14), (a76, b5, c1,d15), (a76, b5, c1, d16), (a76, b5, c1, d17), (a76, b5, c1, d18), (a76,b5, c1, d19), (a76, b5, c1, d20), (a76, b5, c1, d21), (a76, b5, c1,d22), (a76, b5, c2, d1), (a76, b5, c2, d2), (a76, b5, c2, d3), (a76, b5,c2, d4), (a76, b5, c2, d5), (a76, b5, c2, d6), (a76, b5, c2, d7), (a76,b5, c2, d3), (a76, b5, c2, d9), (a76, b5, c2, d10), (a76, b5, c2, d11),(a76, b5, c2, d12), (a76, b5, c2, d13), (a76, b5, c2, d14), (a76, b5,c2, d15), (a76, b5, c2, d16), (a76, b5, c2, d17), (a76, b5, c2, d18),(a76, b5, c2, d19), (a76, b5, c2, d20), (a76, b5, c2, d21), (a76, b5,c2, d22), (a76, b5, c3, d1), (a76, b5, c3, d2), (a76, b5, c3, d3), (a76,b5, c3, d4), (a76, b5, c3, d5), (a76, b5, c3, d6), (a76, b5, c3, d7),(a76, b5, c3, d8), (a76, b5, c3, d9), (a76, b5, c3, d10), (a76, b5, c3,d11), (a76, b5, c3, d12), (a76, b5, c3, d13), (a76, b5, c3, d14), (a76,b5, c3, d15), (a76, b5, c3, d16), (a76, b5, c3, d17), (a76, b5, c3,d18), (a76, b5, c3, d19), (a76, b5, c3, d20), (a76, b5, c3, d21), (a76,b5, c3, d22), (a76, b6, c1, d1), (a76, b6, c1, d2), (a76, b6, c1, d3),(a76, b6, c1, d4), (a76, b6, c1, d5), (a76, b6, c1, d6), (a76, b6, c1,d7), (a76, b6, c1, d8), (a76, b6, c1, d9), (a76, b6, c1, d10), (a76, b6,c1, d11), (a76, b6, c1, d12), (a76, b6, c1, d13), (a76, b6, c1, d14),(a76, b6, c1, d15), (a76, b6, c1, d16), (a76, b6, c1, d17), (a76, b6,c1, d18), (a76, b6, c1, d19), (a76, b6, c1, d20), (a76, b6, c1, d21),(a76, b6, c1, d22), (a76, b6, c2, d1), (a76, b6, c2, d2), (a76, b6, c2,d3), (a76, b6, c2, d4), (a76, b6, c2, d5), (a76, b6, c2, d6), (a76, b6,c2, d7), (a76, b6, c2, d8, (a76, b6, c2, d9), (a76, b6, c2, d10), (a76,b6, c2, d11), (a76, b6, c2, d12), (a76, b6, c2, d13), (a76, b6, c2,d14), (a76, b6, c2, d15), (a76, b6, c2, d16), (a76, b6, c2, d17), (a76,b6, c2, d18), (a76, b6, c2, d19), (a76, b6, c2, d20), (a76, b6, c2,d21), (a76, b6, c2, d22), (a76, b6, c3, d1), (a76, b6, c3, d2), (a76,b6, c3, d3), (a76, b6, c3, d4), (a76, b6, c3, d5), (a76, b6, c3, d6),(a76, b6, c3, d7), (a76, b6, c3, d8), (a76, b6, c3, d9), (a76, b6, c3,d10), (a76, b6, c3, d11), (a76, b6, c3, d12), (a76, b6, c3, d13), (a76,b6, c3, d14), (a76, b6, c3, d15), (a76, b6, c3, d16), (a76, b6, c3,d17), (a76, b6, c3, d18), (a76, b6, c3, d19), (a76, b6, c3, d20), (a76,b6, c3, d21), (a76, b6, c3, d22), (a77, b1, c1, d1), (a77, b1, c1, d2),(a77, b1, c1, d3), (a77, b1, c1, d4), (a77, b1, c1, d5), (a77, b1, c1,d6), (a77, b1, c1, d7), (a77, b1, c1, d3), (a77, b1, c1, d9), (a77, b1,c1, d10), (a77, b1, c1, d11), (a77, b1, c1, d12), (a77, b1, c1, d13),(a77, b1, c1, d14), (a77, b1, c1, d15), (a77, b1, c1, d16), (a77, b1,c1, d17), (a77, b1, c1, d18), (a77, b1, c1, d19), (a77, b1, c1, d20),(a77, b1, c1, d21), (a77, b1, c1, d22), (a77, b1, c2, d1), (a77, b1, c2,d2), (a77, b1, c2, d3), (a77, b1, c2, d4), (a77, b1, c2, d5), (a77, b1,c2, d6), (a77, b1, c2, d7), (a77, b1, c2, d8), (a77, b1, c2, d9), (a77,b1, c2, d10), (a77, b1, c2, d11), (a77, b1, c2, d12), (a77, b1, c2,d13), (a77, b1, c2, d14), (a77, b1, c2, d15), (a77, b1, c2, d16), (a77,b1, c2, d17), (a77, b1, c2, d18), (a77, b1, c2, d19), (a77, b1, c2,d20), (a77, b1, c2, d21), (a77, b1, c2, d22), (a77, b1, c3, d1), (a77,b1, c3, d2), (a77, b1, c3, d3), (a77, b1, c3, d4), (a77, b1, c3, d5),(a77, b1, c3, d6), (a77, b1, c3, d7), (a77, b1, c3, d8), (a77, b1, c3,d9), (a77, b1, c3, d10), (a77, b1, c3, d11), (a77, b1, c3, d12), (a77,b1, c3, d13), (a77, b1, c3, d14), (a77, b1, c3, d15), (a77, b1, c3,d16), (a77, b1, c3, d17), (a77, b1, c3, d18), (a77, b1, c3, d19), (a77,b1, c3, d20), (a77, b1, c3, d21), (a77, b1, c3, d22), (a77, b2, c1, d1),(a77, b2, c1, d2), (a77, b2, c1, d3), (a77, b2, c1, d4), (a77, b2, c1,d5), (a77, b2, c1, d6), (a77, b2, c1, d7), (a77, b2, c1, d8), (a77, b2,c1, d9), (a77, b2, c1, d10), (a77, b2, c1, d11), (a77, b2, c1, d12),(a77, b2, c1, d13), (a77, b2, c1, d14), (a77, b2, c1, d15), (a77, b2,c1, d16), (a77, b2, c1, d17), (a77, b2, c1, d18), (a77, b2, c1, d19),(a77, b2, c1, d20), (a77, b2, c1, d21), (a77, b2, c1, d22), (a77, b2,c2, d1), (a77, b2, c2, d2), (a77, b2, c2, d3), (a77, b2, c2, d4), (a77,b2, c2, d5), (a77, b2, c2, d6), (a77, b2, c2, d7), (a77, b2, c2, d8),(a77, b2, c2, d9), (a77, b2, c2, d10), (a77, b2, c2, d11), (a77, b2, c2,d12), (a77, b2, c2, d13), (a77, b2, c2, d14), (a77, b2, c2, d15), (a77,b2, c2, d16), (a77, b2, c2, d17), (a77, b2, c2, d18), (a77, b2, c2,d19), (a77, b2, c2, d20), (a77, b2, c2, d21), (a77, b2, c2, d22), (a77,b2, c3, d1), (a77, b2, c3, d2), (a77, b2, c3, d3), (a77, b2, c3, d4),(a77, b2, c3, d5), (a77, b2, c3, d6), (a77, b2, c3, d7), (a77, b2, c3,d8), (a77, b2, c3, d9), (a77, b2, c3, d10), (a77, b2, c3, d11), (a77,b2, c3, d12), (a77, b2, c3, d13), (a77, b2, c3, d14), (a77, b2, c3,d15), (a77, b2, c3, d16), (a77, b2, c3, d17), (a77, b2, c3, d18), (a77,b2, c3, d19), (a77, b2, c3, d20), (a7, b2, c3, d21), (a77, b2, c3, d22),(a77, b3, c1, d1), (a77, b3, c1, d2), (a77, b3, c1, d3), (a77, b3, c1,d4), (a77, b3, c1, d5), (a77, b3, c1, d6), (a77, b3, c1, d7), (a77, b3,c1, d8), (a77, b3, c1, d9), (a77, b3, c1, d10), (a77, b3, c1, 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b3, c3, d19), (a77, b3, c3, d20), (a77, b3, c3, d21),(a77, b3, c3, d22), (a77, b4, c1, d1), (a77, b4, c1, d2), (a77, b4, c1,d3), (a77, b4, c1, d4), (a77, b4, c1, d5), (a77, b4, c1, d6), (a77, b4,c1, d7), (a77, b4, c1, d8), (a77, b4, c1, d9), (a77, b4, c1, d10), (a77,b4, c1, d11), (a77, b4, c1, d12), (a77, b4, c1, d13), (a77, b4, c1,d14), (a77, b4, c1, d15), (a77, b4, c1, d16), (a77, b4, c1, d17), (a77,b4, c1, d18), (a77, b4, c1, d19), (a77, b4, c1, d20), (a77, b4, c1,d21), (a77, b4, c1, d22), (a77, b4, c2, d1), (a77, b4, c2, d2), (a77,b4, c2, d3), (a77, b4, c2, d4), (a77, b4, c2, d5), (a77, b4, c2, d6),(a77, b4, c2, d7), (a77, b4, c2, d8), (a77, b4, c2, d9), (a77, b4, c2,d10), (a77, b4, c2, d11), (a77, b4, c2, d12), (a77, b4, c2, d13), (a77,b4, c2, d14), (a77, b4, c2, d15), (a77, b4, c2, d16), (a77, b4, c2,d17), (a77, b4, c2, d18), (a77, b4, c2, d19), (a77, b4, c2, d20), (a77,b4, c2, d21), (a77, b4, c2, d22), (a77, b4, c3, d1), (a77, b4, c3, d2),(a77, b4, c3, d3), (a77, b4, c3, d4), (a77, b4, c3, d5), (a77, b4, c3,d6), (a7, b4, c3, d7), (a77, b4, c3, d8), (a77, b4, c3, d9), (a77, b4,c3, d10), (a77, b4, c3, d11), (a77, b4, c3, d12), (a77, b4, c3, d13),(a77, b4, c3, d14), (a77, b4, c3, d15), (a77, b4, c3, d16), (a77, b4,c3, d17), (a77, b4, c3, d18), (a77, b4, c3, d19), (a77, b4, c3, d20),(a77, b4, c3, d21), (a77, b4, c3, d22), (a77, b5, c1, d1), (a77, b5, c1,d2), (a77, b6, c1, d3), (a77, b5, c1, d4), (a77, b5, c1, d5), (a77, b5,c1, d6), (a77, b5, c1, d7), (a77, b5, c1, d8), (a77, b5, c1, d9), (a77,b5, c1, d10), (a77, b5, c1, d11), (a77, b5, c1, d12), (a77, b5, c1,d13), (a77, b5, c1, d14), (a17, b5, c1, d15), (a77, b5, c1, d16), (a77,b5, c1, d17), (a77, b5, d18), (a77, b5, c1, d19), (a77, b5, c1, d20),(a77, b5, c1, d21), (a77, b5, c1, d22), (a77, b5, c2, d1), (a77, b5, c2,d2), (a77, b5, c2, d3), (a77, b5, c2, d4), (a77, b5, c2, d5), (a77, b5,c2, d6), (a77, b5, c2, d7), (a77, b5, c2, d8), (a77, b5, c2, d9), (a77,b5, c2, d10), (a77, b5, c2, d11), (a77, b5, c2, d12), (a77, b5, c2,d13), (a77, US, c2, d14), (a77, b5, c2, d15), (a77, b5, c2, d16), (a77,b5, c2, d17), (a77, b5, c2, d18), (a77, b5, c2, d19), (a77, b5, c2,d20), (a77, b5, c2, d21), (a77, b5, c2, d22), (a77, b5, c3, d1), (a77,b5, c3, d2), (a77, b5, c3, d3), (a77, b5, c3, d4), (a77, b5, c3, d5),(a77, b5, c3, d6), (a77, b5, c3, d7), (a77, b5, c3, d8), (a77, b5, c3,d9), (a77, b5, c3, d10), (a77, b5, c3, d11), (a77, b5, c3, d12), (a77,b5, c3, d13), (a77, b5, c3, d14), (a77, b5, c3, d15), (a77, b5, c3,d16), (a77, b5, c3, d17), (a77, b5, c3, d18), (a77, b5, c3, d19), (a77,b5, c3, d20), (a77, b5, c3, d21), (a77, b5, c3, d22), (a77, b6, c1, d1),(a77, b6, c1, d2), (a77, b6, c1, d3), (a77, b6, c1, d4), (a77, b6, c1,d5), (a77, b6, c1, d6), (a77, b6, c1, d7), (a77, b6, c1, d8), (a77, b6,c1, d9), (a77, c1, d10), (a77, b6, c1, d11), (a77, b6, c1, d12), (a77,b6, c1, d13), (a77, b6, c1, d14), (a77, b6, c1, d15), (a77, b6, c1,d16), (a77, b6, c1, d17), (a77, b6, c1, d18), (a77, b6, c1, d19), (a77,b6, c1, d20), (a77, b6, c1, d21), (a77, b6, c1, d22), (a77, b6, c2, d1),(a77, b6, c2 d2), (a77, b6, c2, d3), (a77, b6, c2, d4), (a77, b6, c2,d5), (a77, b6, c2, d6), (a77, b6, c2, d7), (a77, b6, c2, d8), (a77, b6,c2, d9), (a77, b6, c2, d10), (a77, b6, c2, d11), (a77, b6, c2, d12),(a77, b6, c2, d13), (a77, b6, c2, d14), (a77, b6, c2, d15), (a77, b6,c2, d10), (a77, b6, c2, d17), (a77, b6, c2, d18), (a77, b6, c2, d19),(a77, b6, c2, d20), (a77, b6, c2, d21), (a77, b6, c2, d22), (a77, b6,c3, d1), (a77, b6, c3, d2), (a77, b6, c3, d3), (a77, b6, c3, d4), (a77,b6, c3, d5), (a77, b6, c3, d6), (a77, b6, c3, d7), (a77, b6, c3, d8),(a77, b6, c3, d9), (a77, b6, c3, d10), (a77, b6, c3, d11), (a77, b6, c3,d12), (a77, b6, c3, d13), (a77, b6, c3, d14), (a77, b6, c3, d15), (a77,b6, c3, d16), (a77, b6, c3, d17), (a77, b6, c3, d18), (a77, b6, c3,d19), (a77, b6, c3, d20), (a77, b6, c3, d21), (a77, b6, c3, d22), (a78,b1, c1, d11), (a78, b1, c1, d2), (a78, b1, c1, d3), (a78, b1, c1, d4),(a78, b1, c1, d5), (a78, b1, c1, d6), (a78, b1, c1, d7), (a78, b1, c1,d8), (a78, b1, c1, d9), (a78, b1, c1, d10), (a78, b1, c1, d11), (a78,b1, c1, d12), (a78, b1, c1, d13), (a78, b1, c1, d14), (a78, b1, c1,d15), (a78, b1, c1, d16), (a78, b1, c1, d17), (a78, b1, c1, d18), (a78,b1, c1, d19), (a78, b1, c1, d20), (a78, b1, c1, d21), (a78, b1, c1,d22), (a78, b1, c2, d1), (a78, b1, c2, d2), (a78, b1, c2, d3), (a78, b1,c2, d4), (a78, b1, c2, d5), (a78, b1, c2, d6), (a78, b1, c2, d7), (a78,b1, c2, d8), (a78, b1, c2, d9), (a78, b1, c2, d10), (a78, b1, c2, (a78,b1, c2, d16), (a78, b1, c1, d17), (a78, b1, c2, d18), (a78, b1, c2,d19), (a78, b1, c2, d20), (a78, b1, c2, d21), (a78, b1, c2, d22), (a78,b1, c3, d1), (a78, b1, c3, d2), (a78, b1, c3, d13), (a78, b1, c3, d4),(a78, b1, c3, d5), (a78, b1, c3, d6), (a78, b1, c3, d7), (a78, b1, c3,d8), (a78, b1, c3, d9), (a78, b1, c3, d10), (a78, b1, c3, d11), (a78,b1, c3, d12), (a78, b1, c3, d13), (a78, b1, c3, d14), (a78, b1, c3,d15), (a78, b1, c3, d16), (a78, b1, c3, d17), (a78, b1, c3, d18), (a78,b1, c3, d19), (a78, b1, c3, d20), (a78, b1, c3, d21), (a78, b1, c3,d22), (a78, b2, c1, d1), (a78, b2, c1, d2), (a78, b2, c1, d3), (a78, b2,c1, d4), (a78, b2, c1, d5), (a78, b2, c1, d6), (a78, b2, c1, d7), (a78,b2, c1, d8), (a78, b2, c1, d9), (a78, b2, c1, d10), (a78, b2, c1, d11),(a78, b2, c1, d12), (a78, b2, c1, d13), (a78, b2, c1, d14), (a78, b2,c1, d15), (a78, b2, c1, d16), (a78, b2, c1, d17), (a78, b2, c1, d18),(a78, b2, c1, d19), (a78, b2, c1, d20), (a78, b2, c1, d21), (a78, b2,c1, d22), (a78, b2, c2, d1), (a78, b2, c2, d2), (a78, b2, c2, d3), (a78,b2, c2, d4), (a78, b2, c2, d5), (a78, b2, c2, d6), (a78, b2, c2, d7),(a78, b2, c2, d8), (a78, b2, c2, d9), (a78, b2, c2, d10), (a78, b2, c2,d11), (a78, b2, c2, d12), (a78, b2, c2, d13), (a78, b2, c2, d14), (a78,b2, c2, d15), (a78, b2, c2, d16), (a78, b2, c2, d17), (a78, b2, c2,d18), (a78, b2, c2, d19), (a78, b2, c2, d20), (a78, b2, c2, d21), (a78,b2, c2, d22), (a78, b2, c3, d1), (a78, b2, c3, d2), (a78, b2, c3, d3),(a78, b2, c3, d4), (a78, b2, c3, d5), (a78, b2, c3, d6), (a78, b2, c3,d7), (a78, b2, c3, d8), (a78, b2, c3, d9), (a78, b2, c3, d10), (a78, b2,c3, d11), (a78, b2, c3, d12), (a78, b2, c3, d13), (a78, b2, c3, d14),(a78, b2, c3, d15), (a78, b2, c3, d16), (a78, b2, c3, d17), (a78, b2,c3, d18), (a78, b2, c3, d19), (a78, b2, c3, d20), (a78, b2, c3, d21),(a78, b2, c3, d22), (a78, b3, c1, d1), (a78, b3, c1, d2), (a78, b3, c1,d3), (a78, b3, c1, d4), (a78, b3, c1, d5), (a78, b3, c1, d6), (a78, b3,c1, d7), (a78, b3, c1, d8), (a78, b3, c1, d9), (a78, b3, c1, d10), (a78,b3, c1, d11), (a78, b3, c1, d12), (a78, b3, c1, d13), (a78, b3, c1,d14), (a78, b3, c1, d15), (a78, b3, c1, d16), (a78, b3, c1, d17), (a78,b3, c1, d18), (a78, b3, c1, d19), (a78, b3, c1, d20), (a78, b3, c1,d21), (a78, b3, c1, d22), (a78, b3, c2, d1), (a78, b3, c2, d2), (a78,b3, c2, d3), (a78, b3, c2, d4), (a78, b3, c2, d5), (a78, b3, c2, d6),(a78, b3, c2, d7), (a78, b3, c2, d8), (a78, b3, c2, d9), (a78, b3, c2,d10), (a78, b3, c2, d11), (a78, b3, c2, d12), (a78, b3, c2, d13), (a78,b3, c2, d14), (a78, b3, c2, d15), (a78, b3, c2, d16), (a78, b3, c2,d17), (a78, b3, c2, d18), (a78, b3, c2, d19), (a78, b3, c2, d20), (a78,b3, c2, d21), (a78, b3, c2, d22), (a78, b3, c3, d1), (a78, b3, c3, d2),(a78, b3, c3, d3), (a78, b3, c3, d4), (a78, b3, c3, d5), (a78, b3, c3,d6), (a78, b3, c3, d7), (a78, b3, c3, d8), (a78, b3, c3, d9), (a78, b3,c3, d10), (a78, b3, c3, d11), (a78, b3, c3, d12), (a78, b3, c3, d13),(a78, b3, c3, d14), (a78, b3, c3, d15), (a78, b3, c3, d16), (a78, b3,c3, d17), (a78, b3, c3, d18), (a78, b3, c3, d19), (a78, b3, c3, d20),(a78, b3, c3, d21), (a78, b3, c3, d22), (a78, b4, c1, d1), (a78, b4, c1,d2), (a78, b4, c1, d3), (a78, b4, c1, d4), (a78, b4, c1, d5), (a78, b4,c1, d6), (a78, b4, c1, d7), (a78, b4, c1, d8), (a78, b4, c1, d9), (a78,b4, c1, d10), (a78, b4, c1, d11), (a78, b4, c1, d12), (a78, b4, c1,d13), (a78, b4, c1, d14), (a78, b4, c1, d15), (a78, b4, c1, d16), (a78,b4, c1, d17), (a78, b4, c1, d18), (a78, b4, c1, d19), (a78, b4, c1,d20), (78, b4, c1, d21), (a78, b4, c1, d22), (a78, b4, c2, d1), (a78,b4, c2, d2), (a78, b4, c2, d3), (a78, b4, c2, d4), (a78, b4, c2, d5),(a78, b4, c2, d6), (a78, b4, c2, d7), (a78, b4, c2, d8), (a78, b4, c2,d9), (a78, b4, c2, d10), (a78, b4, c2, d11), (a78, b4, c2, d12), (a78,b4, c2, d13), (a78, b4, c2, d14), (a78, b4, c2, d15), (a78, b4, c2,d16), (a78, b4, c2, d17), (a78, b4, c2, d18), (a78, b4, c2, d19), (a78,b4, c2, d20), (a78, b4, c2, d21), (a78, b4, c2, d22), (a78, b4, c3, d1),(a78, b4, c3, d2), (a78, b4, c3, d3), (a78, b4, c3, d4), (a78, b4, c3,d5), (a78, b4, c3, d6), (a78, b4, c3, d7), (a78, b4, c3, d8), (a78, b4,c3, d9), (a78, b4, c3, d10), (a78, b4, c3, d11), (a78, b4, c3, d12),(a78, b4, c3, d13), (a78, b4, c3, d14), (a78, b4, c3, d15), (a78, b4,c3, d16), (a78, b4, c3, d17), (a78, b4, c3, d18), (a78, b4, c3, d19),(a78, b4, c3, d20), (a78, b4, c3, d21), (a78, b4, c3, d22), (a78, b5,c1, d1), (a78, b5, c1, d2), (a78, b5, c1, d3), (a78, b5, c1, d4), (a78,b5, c1, d5), (a78, b5, c1, d6), (a78, b5, c1, d7), (a78, b5, c1, d8),(a78, b5, c1, d9), (a78, b5, c1, d10), (a78, b5, c1, d11), (a78, b5, c1,d12), (a78, b5, c1, d13), (a78, b5, c1, d14), (a78, b5, c1, d15), (a78,b5, c1, d16), (a78, b5, c1, d17), (a78, b5, c1, d18), (a78, b5, c1,d19), (a78, b5, c1, d20), (a78, b5, c1, d21), (a78, b5, c1, d22), (a78,b5, c2, d1), (a78, b5, c2, d2), (a78, b5, c2, d3), (a78, b5, c2, d4),(a78, b5, c2, d5), (a78, b5, c2, d6), (a78, b5, c2, d7), (a78, b5, c2,d8), (a78, b5, c2, d9), (a78, b5, c2, d10), (a78, b5, c2, d11), (a78,b5, c2, d12), (a78, b5, c2, d13), (a78, b5, c2, d14), (a78, b5, c2,d15), (a78, b5, c2, d16), (a78, b5, c2, d17), (a78, b5, c2, d18), (a78,b5, c2, d19), (a78, b5, c2, d20), (a78, b5, c2, d21), (a78, b5, c2,d22), (a78, b5, c3, d1), (a78, b5, c3, d2), (a78, b5, c3, d3), (a78, b5,c3, d4), (a78, b5, c3, d5), (a78, b5, c3, d6), (a78, b5, c3, d7), (a78,b5, c3, d8), (a78, b5, c3, d9), (a78, b5, c3, d10), (a78, b5, c3, d11),(a78, b5, c3, d12), (a78, b5, c3, d13), (a78, b5, c3, d14), (a78, b5,c3, d15), (a78, b5, c3, d16), (a78, b5, c3, d17), (a78, b5, c3, d18),(a78, b5, c3, d19), (a78, b5, c3, d20), (a78, b5, c3, d21), (a78, b5,c3, d22), (a78, b6, c1, d1), (a78, b6, c1, d2), (a78, b6, c1, d3), (a78,b6, c1, d4), (a78, b6, c1, d5), (a78, b6, c1, d6), (a78, b6, c1, d7),(a78, b6, c1, d8), (a78, b6, c1, d9), (a78, b6, c1, d10), (a78, b6, c1,d11), (a78, b6, c1, d12), (a78, b6, c1, d13), (a78, b6, c1, d14), (a78,b6, c1, d15), (a78, b6, c1, d16), (a78, b6, c1, d17), (a78, b6, c1,d18), (a78, b6, c1, d19), (a78, b6, c1, d20), (a78, b6, c1, d21), (a78,b6, c1, d22), (a78, b6, c2, d1), (a78, b6, c2, d2), (a78, b6, c2, d3),(a78, b6, c2, d4), (a78, b6, c2, d5), (a78, b6, c2, d6), (a78, b6, c2,d7), (a78, b6, c2, d8), (a78, b6, c2, d9), (a78, b6, c2, d16), (a78, b6,c2, d17), (a78, b6, c2, d12), (a78, b6, c2, d13), (a78, b6, c2, d14),(a78, b6, c2, d15), (a78, b6, c2, d16), (a78, b6, c2, d17), (a78, b6,c2, d18), (a78, b6, c2, d19), (a78, b6, c2, d20), (a78, b6, c2, d21),(a78, b6, c2, d22), (a78, b6, c3, d1), (a78, b6, c3, d2), (a78, b6, c3,d3), (a78, b6, c3, d4), (a78, b6, c3, d15), (a78, b6, c3, d16), (a78,b6, c3, d7), (a78, b6, c3, d8), (a78, b6, c3, d9), (a78, b6, c3, d10),(a78, b6, c3, d11), (a78, b6, c3, d12), (a78, b6, c3, d13), (a78, b6,c3, d14), (a78, b6, c3, d15), (a78, b6, c3, d16), (a78, b6, c3, d17),(a78, b6, c3, d18), (a78, b6, c3, d19), (a78, b6, c3, d20), (a78, b6,c3, d21), (a78, b6, c3, d22), (a79, b1, c1, d1), (a79, b1, c1, d2),(a79, b1, c1, d3), (a79, b1, c1, d4), (a79, b1, c1, d5), (a79, b1, c1,d6), (a79, b1, c1, d7), (a79, b1, c1, d8), (a79, b1, c1, d9), (a79, b1,c1, d10), (a79, b1, c1, d11), (a79, b1, c1, d12), (a79, b1, c1, d13),(a79, b1, c1, d14), (a79, b1, c1, d15), (a79, b1, c1, d16), (a79, b1,c1, d17), (a79, b1, c1, d18), (a79, b1, c1, d19), (a79, b1, c1, d20),(a79, b1, c1, d21), (a79, b1, c1, d22), (a79, b1, c2, d1), (a79, b1, c2,d2), (a79, b1, c2, d3), (a79, b1, c2, d4), (a79, b1, c2, d5), (a79, b1,c2, d6), (a79, b1, c2, d7), (a79, b1, c2, d8), (a79, b1, c2, d9), (a79,b1, c2, d10), (a79, b1, c2, d11), (a79, b1, c2, d12), (a79, b1, c2,d13), (a79, b1, c2, d14), (a79, b1, c2, d15), (a79, b1, c2, d16), (a79,b1, c2, d17), (a79, b1, c2, d18), (a79, b1, c2, d9), (a79, b1, c2, d20),(a79, b1, c2, d21), (a79, b1, c2, d22), (a79, b1, c3, d7), (a79, b1, c3,b1, c3, d7), (a79, b1, c3, d8), (a79, b1, c3, d9), (a79, b1, c3, d10),(a79, b1, c3, d11), (a79, b1, c3, d12), (a79, b1, c3, d13), (a79, b1,c3, d14), (a79, b1, c3, d15), (a79, b1, c3, d16), (a79, b1, c3, d17),(a79, b1, c3, d18), (a79, b1, c3, d19), (a79, b1, c3, d20), (a79, b1,c3, d21), (a79, b1, c3, d22), (a79, b2, c1, d1), (a79, b2, c1, d2),(a79, b2, c1, d3), (a79, b2, c1, d4), (a79, b2, c1, d5), (a79, b2, c1,d6), (a79, b2, c1, d7), (a79, b2, c1, d8), (a79, b2, c1, d9), (a79, b2,c1, d10), (a79, b2, c1, d11), (a79, b2, c1, d12), (a79, b2, c1, d13),(a79, b2, c1, d14), (a79, b2, c1, d15), (a79, b2, c1, d16), (a79, b2,c1, d17), (a79, b2, c1, d18), (a79, b2, c1, d19), (a79, b2, c1, d20),(a79, b2, c1, d21), (a79, b2, c1, d22), (a79, b2, c2, d1), (a79, b2, c2,d2), (a79, b2, c2, d3), (a79, b2, c2, d4), (a79, b2, c2, d5), (a79, b2,c2, d6), (a79, b2, c2, d7), (a79, b2, c2, d8), (a79, b2, c2, d9), (a79,b2, c2, d10), (a79, b2, c2, d11), (a79, b2, c2, d12), (a79, b2, c2,d13), (a79, b2, c2, d14), (a79, b2, c2, d15), (a79, b2, c2, d16), (a79,b2, c2, d17), (a79, b2, c2, d18), (a79, b2, c2, d19), (a79, b2, c2,d20), (a79, b2, c2, d21), (a79, b2, c2, d22), (a79, b2, c3, d1), (a79,b2, c3, d2), (a79, b2, c3, d3), (a79, b2, c3, d4), (a79, b2, c3, d5),(a79, b2, c3, d6), (a79, b2, c3, d7), (a79, b2, c3, d8), (a79, b2, c3,d9), (a79, b2, c3, d10), (a79, b2, c3, d11), (a79, b2, c3, d12), (a79,b2, c3, d13), (a79, b2, c3, d14), (a79, b2, c3, d15), (a79, b2, c3,d16), (a79, b2, c3, d17), (a79, b2, c3, d18), (a79, b2, c3, d19), (a79,b2, c3, d20), (a79, b2, c3, d21), (a79, b2, c3, d22), (a79, b3, c1, d1),(a79, b3, c1, d2), (a79, b3, c1, d3), (a79, b3, c1, d4), (a79, b3, c1,d5), (a79, b3, c1, d6), (a79, b3, c1, d7), (a79, b3, c1, d8), (a79, b3,c1, d9), (a79, b3, c1, d10), (a79, b3, c1, d11), (a79, b3, c1, d12),(a79, b3, c1, d13), (a79, b3, c1, d14), (a79, b3, c1, d15), (a79, b3,c1, d16), (a79, b3, c1, d17), (a79, b3, c1, d18), (a79, b3, c1, d19),(a79, b3, c1, d20), (a79, b3, c1, d21), (a79, b3, c1, d22), (a79, b3,c2, d1), (a79, b3, c2, d2), (a79, b3, c2, d3), (a79, b3, c2, d4), (a79,b3, c2, d5), (a79, b3, c2, d6), (a79, b3, c2, d7), (a79, b3, c2, d8),(a79, b3, c2, d9), (a79, b3, c2, d10), (a79, b3, c2, d11), (a79, b3, c2,d12), (a79, b3, c2, d13), (a79, b3, c2, d14), (a79, b3, c2, d15), (a79,b3, c2, d16), (a79, b3, c2, d17), (a79, b3, c2, d18), (a79, b3, c2,d19), (a79, b3, c2, d20), (a79, b3, c2, d21), (a79, b3, c2, d22), (a79,b3, c3, d1), (a79, b3, c3, d2), (a79, b3, c3, d3), (a79, b3, c3, d4),(a79, b3, c3, d5), (a79, b3, c3, d6), (a79, b3, c3, d7), (a79, b3, c3,d8), (a79, b3, c3, d9), (a79, b3, c3, d10), (a79, b3, c3, d11), (a79,b3, c3, d12), (a79, b3, c3, d13), (a79, b3, c3, d14), (a79, b3, c3,d15), (a79, b3, c3, d16), (a79, b3, c3, d17), (a79, b3, c3, d18), (a79,b3, c3, d19), (a79, b3, c3, d20), (a79, b3, c3, d21), (a79, b3, c3,d22), (a79, b4, c1, d1), (a79, b4, c1, d2), (a79, b4, c1, d3), (a79, b4,c1, d4), (a79, b4, c1, d5), (a79, b4, c1, d6), (a79, b4, c1, d7), (a79,b4, c1, d8), (a79, b4, c1, d9), (a79, b4, c1, d10), (a79, b4, c1, d11),(a79, b4, c1, d12), (a79, b4, c1, d13), (a79, b4, c1, d14), (a79, b4,c1, d15), (a79, b4, c1, d16), (a79, b4, c1, d17), (a79, b4, c1, d18),(a79, b4, c1, d19), (a79, b4, c1, d20), (a79, b4, c1, d21), (a79, b4,c1, d22), (a79, b4, c2, d1), (a79, b4, c2, d2), (a79, b4, c2, d3), (a79,b4, c2, d4), (a79, b4, c2, d5), (a79, b4, c2, d6), (a79, b4, c2, d7),(a79, b4, c2, d8), (a79, b4, c2, d9), (a79, b4, c2, d10), (a79, b4, c2,d11), (a79, b4, c2, d12), (a79, b4, c2, d13), (a79, b4, c2, d14), (a79,b4, c2, d15), (a79, b4, c2, d16), (a79, b4, c2, d17), (a79, b4, c2,d18), (a79, b4, c2, d19), (a79, b4, c2, d20), (a79, b4, c2, d21), (a79,b4, c2, d22), (a79, b4, c3, d1), (a79, b4, c3, d2), (a79, b4, c3, d3),(a79, b4, c3, d4), (a79, b4, c3, d5), (a79, b4, c3, d6), (a79, b4, c3,d7), (a79, b4, c3, d8), (a79, b4, c3, d9), (a79, b4, c3, d10), (a79, b4,c3, d11), (a79, b4, c3, d12), (a79, b4, c3, d13), (a79, b4, c3, d14),(a79, b4, c3, d15), (a79, b4, c3, d16), (a79, b4, c3, d17), (a79, b4,c3, d18), (a79, b4, c3, d19), (a79, b4, c3, d20), (a79, b4, c3, d21),(a79, b4, c3, d22), (a79, b5, c1, d1), (a79, b5, c1, d2), (a79, b5, c1,d3), (a79, b5, c1, d4), (a79, b5, c1, d5), (a79, b5, c1, d6), (a79, b5,c1, d7), (a79, b5, c1, d8), (a79, b5, c1, d9), (a79, b5, c1, d10), (a79,b5, c1, d11), (a79, b5, c1, d12), (a79, b5, c1, d13), (a7, b5, c1, d14),(a79, b5, c1, d15), (a79, b5, c1, d16), (a79, b5, c1, d17), (a79, b5,c1, d18), (a79, b5, c1, d19), (a79, b5, c1, d20), (a79, b5, c1, d21),(a79, b5, c1, d22), (a79, b5, c2, d1), (a79, b5, c2, d2), (a79, b5, c2,d3), (a79, b5, c2, d4), (a79, b5, c2, d5), (a79, b5, c2, d6), (a79, b5,c2, d7), (a79, b5, c2, d8), (a79, b5, c2, d9), (a79, b5, c2, d10), (a79,b5, c2, d11), (a79, b5, c2, d12), (a79, b5, c2, d13), (a79, b5, c2,d14), (a79, b5, c2, d15), (a79, b5, c2, d16), (a79, b5, c2, d17), (a79,b5, c2, d18), (a79, b5, c2, d19), (a79, b5, c2, d20), (a79, b5, c2,d21), (a79, b5, c2, d22), (a79, b5, c3, d1), (a79, b5, c3, d2), (a79,b5, c3, d3), (a79, b5, c3, d4), (a79, b5, c3, d5), (a79, b5, c3, d6),(a79, b5, c3, d7), (a79, b5, c3, d8), (a79, b5, c3, d9), (a79, b5, c3,d10), (a79, b5, c3, d11), (a79, b5, c3, d12), (a79, b5, c3, d13), (a79,b5, c3, d14), (a79, b5, c3, d15), (a79, b5, c3, d16), (a79, b5, c3,d17), (a79, b5, c3, d18), (a79, b5, c3, d19), (a79, b5, c3, d20), (a79,b5, c3, d21), (a79, b5, c3, d22), (a79, b6, c1, d1), (a79, b6, c1, d2),(a79, b6, c1, d3), (a79, b6, c1, d4), (a79, b6, c1, d5), (a79, b6, c1,d6), (a79, b6, c1, d7), (a79, b6, c1, d8), (a79, b6, c1, d9), (a79, b6,c1, d10), (a79, b6, c1, d11), (a79, b6, c1, d12), (a79, b6, c1, d13),(a79, b6, c1, d14), (a79, b6, c1, d15), (a79, b6, c1, d16), (a79, b6,c1, d17), (a79, b6, c1, d18), (a79, b6, c1, d19), (a79, b6, c1, d20),(a79, b6, c1, d21), (a79, b6, c1, d22), (a79, b6, c2, d1), (a79, b6, c2,d2), (a79, b6, c2, d3), (a79, b6, c2, d4), (a79, b6, c2, d5), (a79, b6,c2, d6), (a79, b6, c2, d7), (a79, b6, c2, d8), (a79, b6, c2, d9), (a79,b6, c2, d10), (a79, b6, c2, d11), (a79, b6, c2, d12), (a79, b6, c2,d13), (a79, b6, c2, d14), (a79, b6, c2, d15), (a79, b6, c2, d16), (a79,b6, c2, d17), (a79, b6, c2, d18), (a79, b6, c2, d19), (a79, b6, c2,d20), (a79, b6, c2, (d21), (a79, b6, c2, d22), (a79, b6, c3, d1), (a79,b6, c3, d2), (a79, b6, c3, d3), (a79, b6, c3, d4), (a79, b6, c3, d5),(a79, b6, c3, d6), (a79, b6, c3, d7), (a79, b6, c3, d8), (a79, b6, c3,d9), (a79, b6, c3, d10), (a79, b6, c3, d11), (a79, b6, c3, d12), (a79,b6, c3, d13), (a79, b6, c3, d14), (a79, b6, c3, d15), (a79, b6, c3,d16), (a79, b6, c3, d17), (a79, b6, c3, d18), (a79, b6, c3, d19), (a79,b6, c3, d20), (a79, b6, c3, d21), (a79, b6, c3, d22), (a80, b1, c1, d1),(a80, b1, c1, d2), (a80, b1, c1, d3), (a80, b1, c1, d4), (a80, b1, c1,d5), (a80, b1, c1, d6), (a80, b1, c1, d7), (a80, b1, c1, d8), (a80, b1,c3, d9), (a80, b1, c1, d10), (a80, b1, c1, d11), (a80, b1, c1, d12),(a80, b1, c1, d13), (a80, b1, c1, d14), (a80, b1, c1, d15), (a80, b1,c1, d16), (a80, b1, c1, d17), (a80, b1, c1, d18), (a80, b1, c1, d19),(a80, b1, c1, d20), (a80, b1, c1, d21), (a80, b1, c1, d22), (a80, b1,c2, d1), (a80, b1, c2, d2), (a80, b1, c2, d3), (a80, b1, c2, d4), (a80,b1, c2, d5), (a80, b1, c2, d6), (a80, b1, c2, d7), (a80, b1, c2, d8),(a80, b1, c2, d9), (a80, b1, c2, d10), (a80, b1, c2, d11), (a80, b1, c2,d12), (a80, b1, c2, d13), (a80, b1, c2, d14), (a80, b1, c2, d15), (a80,b1, c2, d16), (a80, b1, c2, d17), (a80, b1, c2, d18), (a80, b1, c2,d19), (a80, b1, c2, d20), (a80, b1, c2, d21), (a80, b1, c2, d22), (a80,b1, c3, d1), (a80, b1, c3, d2), (a80, b1, c3, d3), (a80, b1, c3, d4),(a80, b1, c3, d5), (a80, b1, c3, d6), (a80, b1, c3, d7), (a80, b1, c3,d8), (a80, b1, c3, d9), (a80, b1, c3, d10), (a80, b1, c3, d11), (a80,b1, c3, d12), (a80, b1, c3, d13), (a80, b1, c3, d14), (a80, b1, c3,d15), (a80, b1, c3, d16), (a80, b1, c3, d17), (a80, b1, c3, d18), (a80,b1, c3, d19), (a80, b1, c3, d20), (a80, b1, c3, d21), (a80, b1, c3,d22), (a80, b2, c1, d1), (a80, b2, c1, d2), (a80, b2, c1, d3), (a80, b2,c1, d4), (a80, b2, c1, d5), (a80, b2, c1, d6), (a80, b2, c1, d7), (a80,b2, c1, d8), (a80, b2, c1, d9), (a80, b2, c1, d10), (a80, b2, c1, d11),(a80, b2, c1, d12), (a80, b2, c1, d13), (a80, b2, c1, d14), (a80, b2,c1, d15), (a80, b2, c1, d16), (a80, b2, c1, d17), (a80, b2, c1, d18),(a80, b2, c1, d19), (a80, b2, c1, d20), (a80, b2, c1, d21), (a80, b2,c1, d22), (a80, b2, c2, d1), (a80, b2, c2, d2), (a80, b2, c2, d3), (a80,b2, c2, d4), (a80, b2, c2, d5), (a80, b2, c2, d6), (a80, b2, c2, d7),(a80, b2, c2, d8), (a80, b2, c2, d9), (a80, b2, c2, d10), (a80, b2, c2,d11), (a80, b2, c2, d12), (a80, b2, c2, d13), (a80, b2, c2, d14), (a80,b2, c2, d15), (a80, b2, c2, d16), (a80, b2, c2, d17), (a80, b2, c2,d18), (a80, b2, c2, d19), (a80, b2, c2, d20), (a80, b2, c2, d21), (a80,b2, c2, d22), (a80, b2, c3, d1), (a80, b2, c3, d2), (a80, b2, c3, d3),(a80, b2, c3, d4), (a80, b2, c3, d5), (a80, b2, c3, d6), (a80, b2, c3,d7), (a80, b2, c3, d8), (a80, b2, c3, d9), (a80, b2, c3, d10), (a80, b2,c3, d11), (a80, b2, c3, d12), (a80, b2, c3, d13), (a80, b2, c3, d14),(a50, b2, c3, d15), (a80, b2, c3, d16), (a80, b2, c3, d17), (a80, b2,c3, d18), (a80, b2, c3, d19), (a80, b2, c3, d20), (a80, b2, c3, d21),(a80, b2, c3, d22), (a80, b3, c1, d1), (a80, b3, c1, d2), (a80, b3, c1,d3), (a80, b3, c1, d4), (a80, b3, c1, d5), (a80, b3, c1, d6), (a80, b3,c1, d7), (a80, b3, c1, d8), (a50, b3, c1, d9), (a80, b3, c1, d10), (a80,b3, c1, d11), (a80, b3, c1, d12), (a80, b3, c1, d13), (a80, b3, c1,d14), (a80, b3, c1, d15), (a80, b3, c1, die), (a80, b3, c1, d17), (a80,b3, c1, d18), (a80, b3, c1, d19), (a80, b3, c1, d20), (a80, b3, c1,d21), (a80, b3, c1, d22), (a50, b3, c2, d1), (a80, b3, c2, d2), (a80,b3, c2, d3), (a80, b3, c2, d4), (a80, b3, c2, d5), (a80, b3, c2, d6),(a80, b3, c2, d7), (a80, b3, c2, d8), (a80, b3, c2, d9), (a80, b3, c2,d10), (a80, b3, c2, d11), (a80, b3, c2, d12), (a80, b3, c2, d13), (a80,b3, c2, d14), (a80, b3, c2, d15), (a80, b3, c2, d16), (a80, b3, c2,d17), (a80, b3, c2, d18), (a80, b3, c2, d19), (a80, b3, c2, d20), (a80,b3, c2, d21), (a80, b3, c2, d22), (a80, b3, c3, d1), (a80, b3, c3, d2),(a80, b3, c3, d3), (a80, b3, c3, d4), (a80, b3, c3, d5), (a50, b3, c3,d6), (a80, b3, c3, d7), (a50, b3, c3, d8), (a80, b3, c3, d9), (a80, b3,c3, d10), (a80, b3, c3, d11), (a80, b3, c3, d12), (a80, b3, c3, d13),(a80, b3, c3, d14), (a80, b3, c3, d15), (a80, b3, c3, d16), (a80, b3,c3, d17), (a80, b3, c3, d18), (a80, b3, c3, d19), (a80, b3, c3, d20),(a80, b3, c3, d21), (a80, b3, c3, d22), (a80, b4, c1, d1), (a80, b4, c1,d2), (a80, b4, c1, d3), (a50, b4, c1, d4), (a80, b4, c1, d5), (a80, b4,c1, d6), (a80, b4, c1, d7), (a80, b4, c1, d8), (a80, b4, c1, d9), (a50,b4, c1, d10), (a80, b4, c1, d11), (a80, b4, c1, d12), (a80, b4, c1,d13), (a80, b4, c1, d14), (a80, b4, c1, d15), (a80, b4, c1, d16), (a80,b4, c1, d17), (a80, b4, c1, d18), (a50, b4, c1, d19), (a80, b4, c1,d20), (a80, b4, c1, d21), (a80, b4, c1, d22), (a80, b4, c2, d1), (a80,b4, c2, d2), (a80, b4, c2, d3), (a80, b4, c2, d4), (a80, b4, c2, d5),(a80, b4, c2, d6), (a80, b4, c2, d7), (a80, b4, c2, d8), (a80, b4, c2,d9), (a80, b4, c2, d10), (a80, b4, c2, d11), (a80, b4, c2, d12), (a80,b4, c2, d13), (a80, b4, c2, d14), (a80, b4, c2, d15), (a80, b4, c2,d16), (a80, b4, c2, d17), (a80, b4, c2, d18), (a80, b4, c2, d19), (a80,b4, c2, d20), (a50, b4, c2, d21), (a80, b4, c2, d22), (a80, b4, c3, d1),(a80, b4, c3, d2), (a80, b4, c3, d3), (a80, b4, c3, d4), (a80, b4, c3,d5), (a80, b4, c3, d6), (a80, b4, c3, d7), (a80, b4, c3, d8), (a80, b4,c3, d9), (a80, b4, c3, d10), (a80, b4, c3, d11), (a80, b4, c3, d12),(a80, b4, c3, d13), (a80, b4, c3, 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b6, c2, d8), (a80, b6, c2, d9), (a80, b6, c2, d10), (a80,b6, c2, d11), (a80, b6, c2, d12), (a80, b6, c2, d13), (a80, b6, c2,d14), (a80, b6, c2, d15), (a80, b6, c2, d16), (a80, b6, c2, d7), (a80,b6, c2, d18), (a80, b6, c2, d19), (a80, b6, c2, d20), (a80, b6, c2,d21), (a80, b6, c2, d22), (a80, b6, c3, d1), (a80, b6, c3, d2), (a80,b6, c3, d3), (a80, b6, c3, d4), (a80, b6, c3, d5), (a80, b6, c3, d6),(a80, b6, c3, d7), (a80, b6, c3, d8), (a80, b6, c3, d9), (a80, b6, c3,d10), (a80, b6, c3, d11), (a80, b6, c3, d12), (a80, b6, c3, d13), (a80,b6, c3, d14), (a80, b6, c3, d15), (a80, b6, c3, d16), (a80, b6, c3,d17), (a80, b6, c3, d18), (a80, b6, c3, d19), (a80, b6, c3, d20), (a80,b6, c3, d21), (a80, b6, c3, d22), (a81, b1, c1, d1), (a81, b1, c1, d2),(a81, b1, c1, d3), (a81, d4), (a81, b1, c1, d5), (a81, b1, c1, d6),(a81, b1, c1, d7), (a81, b1, c1, d8), (a81, b1, c1, d9), (a81, b1, c1,d10), (a81, b1, c1, d11), (a81, b1, c1, d2), (a81, b1, c1, d13), (a81,b1, c1, d14), (a81, b1, c1, d5), (a81, b1, c1, d16), (a81, b1, c1, d17),(a81, b1, c1, d18), (a81, b1, c1, d19), (a81, b1, c1, d20), (a81, b1,c1, d21), (a81, b1, c1, d22), (a81, b1, c2, d1), (a81, b1, c2, d2),(a81, b1, c2, d3), (a81, b1, c2, d4), (a81, b1, c2, d5), (a81, b1, c2,d6), (a81, b1, c2, d7), (a81, b1, c2, d8), (a81, b1, c2, d9), (a81, b1,c2, d10), (a81, b1, c2, d11), (a81, b1, c2, d12), (a81, b1, c2, d3),(a81, b, c2, d14), (a81, b1, c2, d15), (a81, b1, c2, d16), (a81, b1, c2,d17), (a81, b1, c2, d18), (a81, b1, c2, d19), (a81, b1, c2, d20), (a81,b1, c2, d21), (a81, b, c2, d22), (a81, b1, c3, d1), (a81, b1, c3, d2),(a81, b1, c3, d3), (a81, b1, c3, d4), (a81, b1, c3, d5), (a81, b1, c3,d6), (a81, b1, c3, d7), (a81, b1, c3, d8), (a8, b1, c3, d9), (a81, b1,c3, d10), (a81, b1, c3, d11), (a81, b1, c3, d12), (a81, b1, c3, d13),(a81, b1, c3, d14), (a81, b1, c3, d15), (a81, b1, c3, d16), (a81, b1,c3, d17), (a81, b1, c3, d18), (a81, b1, c3, d19), (a81, b1, c3, d20),(a81, b1, c3, d21), (a81, b1, c3, d22), (a81, b2, c1, d1), (a81, b2, c1,d2), (a81, b2, c1, d3), (a81, b2, c1, d4), (a81, b2, c1, d5), (a81, b2,c1, d6), (a81, b2, c1, d7), (a81, b2, c1, d8), (a81, b2, c1, d9), (a81,b2, c1, d10), (a81, b2, c1, d11), (a81, b2, c1, d12), (a81, b2, c1,d13), (a81, b2, c1, d14), (a81, b2, c1, d15), (a81, b2, c1, d16), (a81,b2, c1, d17), (a81, b2, c1, d18), (a81, b2, c1, d19) (a81, b2, c1, d20),(a81, b2, c1, d21), (a81, b2, c1, d22), (a81, b2, c2, d1), (a81, b2, c2,d2), (a81, b2, c2, d3), (a81, b2, c2, d4), (a81, b2, c2, d5), (a81, b2,c2, d6), (a81, b2, c2, d7), (a81, b2, c2, d8), (a81, b2, c2, d9), (a81,b2, c2, d10), (a81, b2, c2, d11), (a81, b2, c2, d12), (a81, b2, c2,d13), (a81, b2, c2, d14), (a81, b2, c2, d15), (a81, b2, c2, d16), (a81,b2, c2, d17), (a81, b2, c2, d18), (a81, b2, c2, d19), (a81, b2, c2,d20), (a81, b2, c2, d21), (a81, b2, c2, d22), (a81, b2, c3, d1), (a81,b2, c3, d2), (a81, b2, c3, d3), (a81, b2, c3, d4), (a81, b2, c3, d5),(a81, b2, c3, d6), (a81, b2, c3, d7), (a81, b2, c3, d8), (a81, b2, c3,d9), (a81, b2, c3, d10), (a81, b2, c3, d11), (a81, b2, c3, d12), (a81,b2, c3, d13), (a81, b2, c3, d14), (a81, b2, c3, d15), (a81, b2, c3,d16), (a81, b2, c3, d17), (a81, b2, c3, d18), (a81, b2, c3, d19), (a81,b2, c3, d20), (a81, b2, c3, d21), (a81, b2, c3, d22), (a81, b3, c1, d1),(a81, b3, c1, d2), (a81, b3, c1, d3), (a81, b3, c1, d4), (a81, b3, c1,d5), (a81, b5, c1, d6), (a81, b3, c1, d7), (a81, b3, c1, d8), (a81, b,c1, d9), (a81, b3, c1, d10), (a81, b3, c1, d11), (a81, b3, c1, d12),(a81, b3, c1, d13), (a81, b3, c1, d14), (a81, b3, c1, d15), (a81, b3,c1, d16), (a81, b3, c1, d17), (a81, b5, c1, d8), (a81, b5, c1, d19),(a81, b3, c1, d20), (a8, b3, c1, d21), (a81, b3, c1, d22), (a81, b3, c2,d1), (a81, b3, c2, d2), (a81, b3, c2, d3), (a81, b3, c2, d4), (a81, b3,c2, d5), (a81, b3, c2, d6), (a81, b3, c2, d7), (a81, b3, c2, d8), (a81,b3, c2, d9), (a81, b3, c2, d1), (a81, b3, c2, d11), (a81, b3, c2, d12),(a81, b3, c2, d13), (a81, b3, c2, d14), (a81, b3, c2, d15), (a81, b3,c2, d16), (a81, b3, c2, d17), (a81, b3, c2, d18), (a81, b3, c2, d19),(a81, b3, c2, d20), (a81, b3, c2, d21), (a81, b3, c2, d22), (a81, b3,c3, d1), (a81, b3, c3, d2), (a81, b3, c3, d3), (a81, b3, c3, d4), (a81,b3, c3, d5), (a81, b3, c3, d6), (a81, b3, c3, d7), (a81, b3, c3, d8),(a81, b3, c3, d9), (a81, b3, c3, d10), (a81, b3, c3, d11), (a81, b3, c1,d12), (a81, b3, c3, d13), (a81, b3, c3, d14), (a81, b3, c3, d15), (a81,b3, c3, d16), (a81, b3, c3, d17), (a81, b3, c3, d18), (a81, b3, c3,d19), (a81, b3, c3, d20), (a81, b3, c3, d21), (a81, b3, c3, d22), (a81,b4, c1, d1), (a81, b4, c1, d2), (a81, b4, c1, d3), (a81, b4, c1, d4),(a81, b4, c1, d5), (a81, b4, c1, d6), (a81, b4, c1, d7), (a81, b4, c1,d8), (a81, b4, c1, d9), (a81, b4, c1, d10), (a81, b4, c1, d11), (a81,b4, c1, d12), (a81, b4, c1, d13), (a81, b4, c1, d14), (a81, b4, c1,d15), (a81, b4, c1, d16), (a81, b4, c1, d17), (a81, b4, c1, d18), (a81,b4, c1, d19), (a81, b4, c1, d20), (a81, b4, c1, d21), (a8, b4, c1, d22),(a81, b4, c2, d1), (a8, b4, c2, d2), (a81, b4, c2, d3), (a81, b4, c2,d4), (a81, b4, c2, d5), (a81, b4, c2, d6), (a81, b4, c2, d7), (a81, b4,c2, d8), (a81, b4, c2, d9), (a81, b4, c2, d10), (a81, b4, c2, d11),(a81, b4, c2, d12), (a81, b4, c2, d13), (a81, b4, c2, d14), (a81, b4,c2, d15), (a81, b4, c2, d16), (a81, b4, c2, d17), (a81, b4, c2, d18),(a81, b4, c2, d19), (a81, b4, c2, c20), (a81, b4, c2, d21), (a81, b4,c2, d22), (a81, b4, c3, d1), (a81, b4, c3, d2), (a81, b4, c3, d3), (a81,b4, c3, d4), (a81, b4, c3, d5), (a8, b4, c3, d6), (a81, b4, c3, d7),(a81, b4, c3, d18), (a81, b4, c3, d9), (a81, b4, c3, d10), (a81, b4, c3,d11), (a81, b4, c3, d12), (a81, b4, c3, d13), (a81, b4, c3, d14), (a81,b4, c3, d15), (a81, b4, c3, d16), (a81, b4, c3, d17), (a81, b4, c3,d18), (a81, b4, c3, d19), (a81, b4, c3, d20), (a81, b4, c3, d21), (a81,b4, c3, d22), (a81, b5, c1, d1), (a81, b5, c1, d2), (a81, b5, c1, d3),(a81, b5, c1, d4), (a81, b5, c1, d5), (a81, b5, c1, d16), (a81, b5, c1,d7), (a81, b5, c1, d8), (a81, b5, c1, d9), (a81, b5, c1, d10), (a81, b5,c1, 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(a81, b5, c3, d19), (a81, b5, c3, d20), (a81,b5, c3, d21), (a81, b5, c3, d22), (a81, b6, c1, d1), (a81, b6, c1, d2),(a81, b1, c1, d3), (a81, b6, c1, d4), (a81, b6, c1, d5), (a81, b6, c1,d6), (a81, b6, c1, d7), (a81, b6, c1, d8), (a81, b6, c1, d9), (a81, b6,c1, d10), (a81, b6, c1, d11), (a81, b6, c1, d11), (a81, b6, b 1, d113),(a81, b6, c1, d14), (a81, b6, c1, d85), (a81, b6, c1, d116), (a81, b3,c1, d117), (a81, b6, c1, d18), (a81, b6, c1, d19), (a81, b6, c1, d20),(a81, b6, c1, d21), (a81, b6, c1, d22), (a81, b6, c2, d1), (a81, b6, c2,d12), (a81, b6, c2, d13), (a81, b6, c2, d14), (a81, b6, c2, d15), (a81,b6, c2, d6), (a81, b6, c2, d7), (a81, b6, c2, d18), (a81, b6, c2, d5),(a81, b6, c2, d10), (a81, b6, c2, d11), (a81, b6, c2, d12), (a81, b6,c2, d13), (a81, b 6, c2, d14), (a81, b6, c2, d15), (a81, b6, c2, d16),(a81, b6, c2, d17), (a81, b3, c2, d18), (a81, b6, c2, d19), (a81, b6,c2, d20), (a81, b6, c2, d21), (a81, b6, c2, d22), (a81, b6, c3, d1),(a81, b6, c3, d2), (a81, b6, c3, d3), (a81, 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(a82, b3, c1, d10), (a82,b3, c1, d11), (a82, b3, c1, d12), (a82, b3, c1, d13), (a82, b3, c1,d14), (a82, b3, c1, d15), (a82, b3, c1, d16), (a82, b3, c1, d17), (a82,b3, c1, d18), (a82, b3, c1, d19), (a82, b3, c1, d20), (a82, b3, c1,d21), (a82, b3, c1, d22), (a82, b3, c2, d1), (a82, b3, c2, d2), (a82,b3, c2, d3), (a82, b3, c2, d4), (a82, b3, c2, d5), (a82, b3, c2, d6),(a82, b3, c2, d7), (a82, b3, c2, d8), (a82, b3, c2, d9), (a82, b3, c2,d10), (a82, b3, c2, d11), (a82, b3, c2, d12), (a82, b3, c2, d13), (a82,b3, c2, d14), (a82, b3, c2, d15), (a82, b3, c2, d16), (a82, b3, c2,d17), (a82, b3, c2, d18), (a82, b3, c2, d19), (a82, b3, c2, d20), (a82,b3, c2, d21), (a82, b3, c2, d22), (a82, b3, c3, d1), (a82, b3, c3, d2),(a82, b3, c3, d3), (a82, b3, c3, d4), (a82, b3, c3, d5), (a82, b3, c3,d6), (a82, b3, c3, d7), (a82, b3, c3, d8), (a82, b3, c3, d9), (a82, b3,c3, d10), (a82, b3, c3, d11), (a82, b3, c3, d12), (a82, b3, c3, d13),(a82, b3, c3, d14), (a82, b3, c3, d15), (a82, b3, c3, d16), (a82, b3,c3, 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c2, d11), (a82,b5, c2, d12), (a82, b5, c2, d13), (a82, b5, c2, d14), (a82, b5, c2,d15), (a82, b5, c2, d16), (a82, b5, c2, d17), (a82, b5, c2, d18), (a82,b5, c2, d19), (a82, b5, c2, d20), (a82, b5, c2, d21), (a82, b5, c2,d22), (a82, b5, c3, d1), (a82, b5, c3, d2), (a82, b5, c3, d3), (a82, b5,c3, d4), (a82, b5, c3, d5), (a82, b5, c3, d6), (a82, b5, c3, d7), (a82,b5, c3, d8), (a82, b5, c3, d9), (a82, b5, c3, d10), (a82, b5, c3, d11),(a82, b5, c3, d12), (a82, b5, c3, d13), (a82, b5, c3, d14), (a82, b5,c3, d15), (a82, b5, c3, d16), (a82, b5, c3, d17), (a82, b5, c3, d18),(a82, b5, c3, d19), (a82, b5, c3, d20), (a82, b5, c3, d21), (a82, b5,c3, d22), (a82, b6, c1, d1), (a82, b6, c1, d2), (a82, b6, c1, d3), (a82,b6, c1, d4), (a82, b6, c1, d5), (a82, b6, c1, d6), (a82, b6, c1, d7),(a82, b6, c1, d8), (a82, bb, c1, d9), (a82, b6, c1, d10), (a82, b6, c1,d11), (a82, b6, c1, d12), (a82, b6, c1, d13), (a82, b6, c1, d14), (a82,b6, c1, d15), (a82, b6, c1, d16), (a82, b6, c1, d17), (a82, b6, c1,d18), (a82, b6, c1, d19), (a82, b6, c1, d20), (a82, b6, c1, d21), (a82,b6, c1, d22), (a82, b6, c2, d1), (a82, b6, c2, (d2), (a82, b6, c2, d3),(a82, bb, c2, d4), (a82, b6, c2, d5), (a82, b6, c2, d6), (a82, b6, c2,d7), (a82, b6, c2, d8), (a82, b6, c2, d9), (a82, b6, c2, d10), (a82, b6,c2, d11), (a82, bb, c2, d12), (a82, b6, c2, d13), (a82, b6, c2, d14),(a82, b6, c2, d15), (a82, b6, c2, d16), (a82, b6, c2, div), (a82, bb,c2, d18), (a82, b6, c2, d19), (a82, b6, c2, d20), (a82, b6, c2, d21),(a82, b6, c2, d22), (a82, b6, c3, d1), (a82, b6, c3, d2), (a82, b6, c3,d3), (a82, b6, c3, d4), (a82, b6, c3, d5), (a82, b6, c3, d6), (a82, b6,c3, d7), (a82, b6, c3, d8), (a82, b6, c3, d9), (a82, b6, c3, d10), (a82,b6, c3, d11), (a82, b6, c3, d12), (a82, b6, c3, d13), (a82, b6, c3,d14), (a82, b6, c3, d15), (a82, b6, c3, d16), (a82, b6, c3, d17), (a82,b6, c3, d18), (a82, b6, c3, d19), (a82, b6, c3, d20), (a82, b6, c3,d21), (a82, b6, c3, d22), (a83, b1, c1, d1), (a83, b1, c1, d2), (a83,b1, c1, d3), (a83, b1, c1, d4), (a83, b1, c1, d5), (a83, b1, c1, d6),(a83, b1, c1, d7), (a83, b1, c1, d8), (a83, b1, c1, d9), (a83, b1, c1,d10), (a83, b1, c1, d11), (a83, b1, c1, d12), (a83, b1, c1, d13), (a83,b1, c1, d14), (a83, b1, c1, d15), (a83, b1, c1, d16), (a83, b1, c1,d17), (a83, b1, c1, d18), (a83, b1, c1, d19), (a83, b1, c1, d20), (a83,b1, c1, d21), (a83, b1, c1, d22), (a83, b1, c2, d1), (a83, b1, c2, d2),(a83, b1, c2, d3), (a83, b1, c2, d4), (a83, b1, c2, d5), (a83, b1, c2,d6), (a83, b1, c2, d7), (a83, b1, c2, d8), (a83, b1, c2, d9), (a83, b1,c2, d10), (a83, b1, c2, d11), (a83, b1, c2, d12), (a83, b1, c2, d13),(a83, b1, c2, d14), (a83, b1, c2, d15), (a83, b1, c2, d16), (a83, b1,c2, d17), (a83, b1, c2, d18), (a83, b1, c2, d19), (a83, b1, c2, d20),(a83, b1, c2, d21), (a83, b1, c2, d22), (a83, b1, c3, d1), (a83, b1, c3,d2), (a83, b1, c3, d3), (a83, b1, c3, d4), (a83, b1, c3, d5), (a83, b1,c3, d6), (a83, b1, c3, d7), (a83, b1, c3, d8), (a83, b1, c3, d9), (a83,b1, c3, d10), (a83, b1, c3, d11), (a83, b1, c3, d12), (a83, b1, c3,d13), (a83, b1, c3, d14), (a83, b1, c3, d15), (a83, b1, c3, d16), (a83,b1, c3, d17), (a83, b1, c3, d18), (a83, b1, c3, d19), (a83, b1, c3,d20), (a83, b1, c3, d21), (a83, b1, c3, d22), (a83, b2, c1, d1), (a83,b2, c1, d2), (a83, b2, c1, d3), (a83, b2, c1, d4), (a83, b2, c1, d5),(a83, b2, c1, d6), (a83, b2, c1, d7), (a83, b2, c1, d8), (a83, b2, c1,d9), (a83, b2, c1, d10), (a83, b2, c1, d11), (a83, b2, c1, d12), (a83,b2, c1, d13), (a83, b2, c1, d14), (a83, b2, c1, d15), (a83, b2, c1,d16), (a83, b2, c1, d17), (a83, b2, c1, d18), (a83, b2, c1, d19), (a83,b2, c1, d20), (a83, b2, c1, d21), (a83, b2, c1, d22), (a83, b2, c2, d1),(a83, b2, c2, d2), (a83, b2, c2, d3), (a83, b2, c2, d4), (a83, b2, c2,d5), (a83, b2, c2, d6), (a83, b2, c2, d7), (a83, b2, c2, d8), (a83, b2,c2, d9), (a83, b2, c2, d10), (a83, b2, c2, d11), (a83, b2, c2, d12),(a83, b2, c2, d13), (a83, b2, c2, d14), (a83, b2, c2, d15), (a83, b2,c2, d16), (a83, b2, c2, d17), (a83, b2, c2, d18), (a83, b2, c2, d19),(a83, b2, c2, d20), (a83, b2, c2, d21), (a8, b2, c2, d22), (a83, b2, c3,d1), (a83, b2, c3, d2), (a83, b2, c3, d3), (a83, b2, c3, d4), (a83, b2,c3, d5), (a83, b2, c3, d6), (a83, b2, c3, d7), (a83, b2, c3, d8), (a83,b2, c3, d9), (a83, b2, c3, d10), (a83, b2, c3, d11), (a83, b2, c3, d12),(a83, b2, c3, d13), (a83, b2, c3, d14), (a83, b2, c3, d15), (a83, b2,c3, d16), (a83, b2, c3, d17), (a83, b2, c3, d18), (a83, b2, c3, d19),(a83, b2, c3, d20), (a83, b2, c3, d21), (a83, b2, c3, d22), (a83, b2,c1, d1), (a83, b3, c1, d2), (a83, b5, c1, d5), (a83, b5, c1, d4), (a83,b5, c1, d5), (a83, b5, c1, d6), (a83, b5, c1, d7), (a83, b3, c1, d8),(a83, b3, c1, d9), (a83, b5, c1, d10), (a83, b3, c1, d11), (a83, b3, c1,d12), (a83, b3, c1, d13), (a83, b5, c1, d14), (a83, b3, c1, d15), (a83,b3, c1, d16), (a83, b5, c1, d17), (a83, b5, c1, d18), (a83, b3, c1,d19), (a83, b3, c1, d20), (a83, b3, c1, d21), (a83, b3, c1, d22), (a83,b3, c2, d1), (a83, b3, c2, d2), (a83, b3, c2, d3), (a83, b5, c2, d4),(a83, b3, c2, d5), (a83, b3, c2, d6), (a83, b3, c2, d7), (a83, b3, c2,d8), (a83, b3, c2, d9), (a83, b3, c2, d10), (a83, b3, c2, d11), (a83,b3, c2, d12), (a83, b3, c2, d13), (a83, b3, c2, d14), (a83, b3, c2,d15), (a83, b3, c2, d16), (a83, b3, c2, d17), (a83, b5, c2, d18), (a83,b3, c2, d19), (a83, b3, c2, d20), (a83, b3, c2, d21), (a83, b3, c2,d22), (a83, b3, c3, d1), (a83, b5, c3, d2), (a83, b3, c3, d3), (a83, b3,c3, d4), (a83, b3, c3, d5), (a83, b5, c3, d6), (a83, b3, c3, d7), (a83,b3, c3, d8), (a83, b5, c3, d9), (a83, b3, c3, d10), (a83, b3, c3, d11),(a83, b3, c3, d12), (a83, b3, c3, d13), (a83, b3, c3, d14), (a83, b3,c3, d15), (a83, b3, c3, d16), (a83, b3, c3, d17), (a83, b3, c3, d18),(a83, b3, c3, d19), (a83, b3, c3, d20), (a83, b3, c3, d21), (a83, b3,c3, d22), (a83, b4, c1, d1), (a83, b4, c1, d2), (a83, b4, c1, d3), (a83,b4, c1, d4), (a83, b4, c1, d5), (a83, b4, c1, d6), (a83, b4, c1, d7),(a83, b4, c1, d8), (a83, b4, c1, d9), (a83, b4, c1, d10), (a83, b4, c1,d11), (a83, b4, c1, d12), (a83, b4, c1, d13), (a83, b4, c1, d14), (a83,b4, c1, d15), (a83, b4, c1, d16), (a83, b4, c1, d17), (a83, b4, c1,d18), (a83, b4, c1, d19), (a83, b4, c1, d20), (a83, b4, c1, d21), (a83,b4, c1, d22), (a83, b4, c2, d1), (a83, b4, c2, d2), (a83, b4, c2, d3),(a83, b4, c2, d4), (a83, b4, c2, d5), (a83, b4, c2, d6), (a83, b4, c2,d7), (a83, b4, c2, d8), (a83, b4, c2, d19), (a83, b4, c2, d10), (a83,b4, c2, d11), (a83, b4, c2, d12), (a83, b4, c2, d13), (a83, b4, c2,d14), (a83, b4, c2, d15), (a83, b4, c2, d16), (a83, b4, c2, d17), (a83,b4, c2, d18), (a83, b4, c2, d19), (a83, b4, c2, d20), (a83, b4, c2,d21), (a83, b4, c2, d22), (a83, b4, c3, d1), (a83, b4, c3, d2), (a83,b4, c3, d3), (a83, b4, c3, d4), (a83, b4, c3, d5), (a83, b4, c3, d6),(a83, b4, c3, d7), (a83, b4, c3, d8), (a83, b4, c3, d9), (a83, b4, c3,d10), (a83, b4, c3, d11), (a83, b4, c3, d12), (a83, b4, c3, d13), (a83,b4, c3, d14), (a83, b4, c3, d15), (a83, b4, c3, d16), (a83, b4, c3,d17), (a83, b4, c3, d18), (a83, b4, c3, d19), (a83, b4, c3, d20), (a83,b4, c3, d21), (a83, b4, c3, d22), (a83, b5, c1, d11), (a83, b5, c1, d2),(a83, b5, c1, d3), (a83, b5, c1, d4), (a83, b5, c1, d5), (a83, b5, c1,d6), (a83, b5, c1, d7), (a83, b5, c1, d8), (a83, b5, c1, d9), (a83, b5,c1, d10), (a53, b5, c1, d11), (a83, b5, c1, d12), (a33, b5, c1, d13),(a83, b5, c1, d14), (a83, b5, c1, d15), (a83, b5, c1, d16), (a83, b5,c1, d17), (a83, b5, c1, d18), (a83, b5, c1, d19), (a83, b5, c1, d20),(a83, b5, c1, d21), (a83, b5, c1, d22), (a83, b5, c2, d1), (a83, b5, c2,d2), (a83, b5, c2, d3), (a83, b5, c2, d4), (a83, b5, c2, d5), (a83, b5,c2, d6), (a83, b5, c2, d7), (a83, b5, c2, d8), (a83, b5, c2, d9), (a83,b5, c2, d10), (a83, b5, c2, d11), (a83, b5, c2, d12), (a83, b5, c2,d13), (a83, b5, c2, d14), (a83, b5, c2, d15), (a83, b5, c2, d16), (a83,b5, c2, d17), (a83, b5, c2, d18), (a53, b5, c2, d19), (a83, b5, c2,d20), (a83, b5, c2, d21), (a83, b5, c2, d22), (a83, b5, c3, d1), (a83,b5, c3, d2), (a83, b5, c3, d3), (a83, b5, c3, d4), (a83, b5, c3, d5),(a83, b5, c3, d6), (a83, b5, c3, d7), (a83, b5, c3, d8), (a53, b5, c3,d9), (a83, b5, c3, d10), (a53, b5, c3, d11), (a83, b5, c3, d12), (a83,b5, c3, d13), (a83, b5, c3, d14), (a83, b5, c3, d15), (a83, b5, c3,d16), (a83, b5, c3, d17), (a83, b5, c3, d18), (a83, b5, c3, d19), (a83,b5, c3, d20), (a83, b5, c3, d21), (a83, b5, c3, d22), (a83, b6, c1, d1),(a83, b6, c1, d2), (a83, b6, c1, d3), (a83, b6, c1, d4), (a83, b6, c1,d5), (a83, b6, c1, d6), (a83, b6, c1, d7), (a83, b6, c1, d8), (a83, b6,c1, d9), (a53, b6, c1, d10), (a83, b6, c1, d11), (a83, b6, c1, d12),(a83, b6, c1, d13), (a83, b6, c1, d14), (a83, b6, c1, d15), (a83, b6,c1, d16), (a83, b6, c1, d17), (a83, b6, c1, d18), (a83, b6, c1, d19),(a83, b6, c1, d20), (a83, b6, c1, d21), (a83, b6, c1, d22), (a83, b6,c2, d1), (a83, b6, c2, d2), (a83, b6, c2, d3), (a83, b6, c2, d4), (a83,b6, c2, d5), (a83, b6, c2, d6), (a83, b6, c2, d7), (a83, b6, c2, d8),(a83, b6, c2, d9), (a53, b6, c2, d10), (a83, b6, c2, d11), (a83, b6, c2,d12), (a53, b6, c2, d13), (a83, b6, c2, d14), (a83, b6, c2, d15), (a83,b6, c2, d16), (a83, b6, c2, d17), (a83, b6, c2, d18), (a83, b6, c2,d19), (a83, b6, c2, d20), (a83, b6, c2, d21), (a83, b6, c2, d22), (a83,b6, c3, d1), (a83, b6, c3, d2), (a83, b6, c3, d3), (a83, b6, c3, d4),(a83, b6, c3, d5), (a83, b6, c3, (d6), (a83, b6, c3, d7), (a83, b6, c3,d8), (a83, b6, c3, d9), (a83, b6, c3, d10), (a83, b6, c3, d11), (a83,b6, c3, d12), (a83, b6, c3, d13), (a83, b6, c3, d14), (a83, b6, c3,d15), (a83, b6, c3, d16), (a83, b6, c3, d17), (a53, b6, c3, d18), (a83,b6, c3, d19), (a83, b6, c3, d20), (a83, b6, c3, d21), (a83, b6, c3,d22), (a84, b1, c1, d1), (a84, b1, c1, d2), (a84, b1, c1, d3), (a84, b1,c1, d4), (a84, b1, c1, d5), (a84, b1, c1, d6), (a84, b1, c1, d7), (a84,b1, c1, d8), (a84, b1, c1, d9), (a84, b1, c1, d10), (a84, b1, c1, d11),(a84, b1, c1, d12), (a84, b1, c1, d13), (a84, b1, c1, d14), (a84, b1,c1, d15), (a84, b1, c1, d10), (a84, b1, c1, d17), (a84, b1, c1, d18),(a84, b1, c1, d19), (a84, b1, c1, d20), (a84, b1, c1, d21), (a84, b1,c1, d22), (a84, b1, c2, d1), (a84, b1, c2, d2), (a84, b1, c2, d3), (a84,b1, c2, d4), (a84, b1, c2, d5), (a84, b1, c2, d6), (a84, b1, c2, d7),(a84, b1, c2, d8), (a84, b1, c2, d9), (a84, b1, c2, d10), (a84, b1, c2,d11), (a84, b1, c2, d12), (a84, b1, c2, d13), (a84, b1, c2, d14), (a84,b1, c2, d15), (a84, b1, c2, d16), (a84, b1, c2, d17), (a84, b1, c2,d18), (a84, b1, c2, d19), (a84, b1, c2, d20), (a84, b1, c2, d21), (a84,b1, c2, d22), (a84, b1, c3, d1), (a84, b1, c3, d2), (a84, b1, c3, d3),(a84, b1, c3, d4), (a84, b1, c3, d5), (a84, b1, c3, d6), (a84, b1, c3,d7), (a84, b1, c3, d8), (a84, b1, c1, d9), (a84, b1, c3, d10), (a84, b1,c3, d11), (a84, b1, c3, d12), (a84, b1, c3, d13), (a84, b1, c3, d14),(a84, b1, c3, d15), (a84, b1, c3, d16), (a84, b1, c3, d17), (a84, b1,c3, d18), (a84, b1, c3, d19), (a84, b1, c3, d20), (a84, b1, c3, d21),(a84, b1, c3, d22), (a84, b2, c1, d1), (a84, b2, c1, d2), (a84, b2, c1,d3), (a84, b2, c1, d4), (a84, b2, c1, d5), (a84, b2, c1, d6), (a84, b2,c1, d7), (a84, b2, c1, d8), (a84, b2, c1, d9), (a84, b2, c1, d10), (a84,b2, c1, d11), (a84, b2, c1, d12), (a84, b2, c1, d13), (a84, b2, c1,d14), (a84, b2, c1, d15), (a84, b2, c1, d16), (a84, b2, c1, d17), (a84,b2, c1, d18), (a84, b2, c1, d19), (a84, b2, c1, d20), (a84, b2, c1,d21), (a84, b2, c1, d22), (a84, b2, c2, d1), (a84, b2, c2, d2), (a84,b2, c2, d3), (a84, b2, c2, d4), (a84, b2, c2, d5), (a84, b2, c2, d6,(a84, b2, c2, d7), (a84, b2, c2, d8), (a84, b2, c2, d9), (a84, b2, c2,d10), (a84, b2, c2, d11), (a84, b2, c2, d12), (a84, b2, c2, d13), (a84,b2, c2, d14), (a84, b2, c2, d15), (a84, b2, c2, d16), (a84, b2, c2,d17), (a84, b2, c2, d18), (a84, b2, c2, d19), (a84, b2, c2, d20), (a84,b2, c2, d21), (a84, b2, c2, d22), (a84, b2, c3, d1), (a84, b2, c3, d2),(a84, b2, c3, d3), (a84, b2, c3, d4), (a84, b2, c3, d5), (a84, b2, c3,d6), (a84, b2, c3, d7), (a84, b2, c3, d8), (a84, b2, c3, d9), (a84, b2,c3, d10), (a84, b2, c3, d11), (a84, b2, c3, d12), (a84, b2, c3, d13),(a84, b2, c3, d14), (a84, b2, c3, d15), (a84, b2, c3, d16), (a84, b2,c3, d17), (a84, b2, c3, d18), (a84, b2, c3, d19), (a84, b2, c3, d20),(a84, b2, c3, d21), (a84, b2, c3, d22), (a84, b3, c1, d1), (a84, b3, c1,d2), (a84, b3, c1, d3), (a84, b5, c1, d4), (a84, b3, c1, d5), (a84, b3,c1, d6), (a84, b3, c1, d7), (a84, b3, c1, d8), (a84, b3, c1, d9), (a84,b3, c1, d10), (a84, b3, c1, d11), (a84, b3, c1, d12), (a84, b3, c1,d13), (a84, b3, c1, d14), (a84, b3, c1, d15), (a84, b3, c1, d16), (a84,b3, c1, d17), (a84, b3, c1, d18), (a84, b3, c1, d19), (a84, b3, c1,d20), (a84, b3, c1, d21), (a84, b3, c1, d22), (a84, b3, c2, d1), (a84,b3, c2, d2), (a84, b3, c2, d3), (a84, b3, c2, d4), (a84, b3, c2, d5),(a84, b3, c2, d6), (a84, b3, c2, d7), (a84, b3, c2, d8), (a84, b3, c2,d9), (a84, b3, c2, d10), (a84, b3, c2, d11), (a84, b3, c2, d12), (a84,b3, c2, d13), (a84, b3, c2, d14), (a84, b5, c2, d15), (a84, b3, c2,d16), (a84, b3, c2, d17), (a84, b3, c2, d18), (a84, b3, c2, d19), (a84,b3, c2, d20), (a84, b3, c2, d21), (a84, b3, c2, d22), (a84, b3, c3, d1),(a84, b3, c3, d2), (a84, b3, c3, d3), (a84, b3, c3, d4), (a84, b3, c3,d5), (a84, b3, c3, d6), (a84, b3, c3, d7), (a84, b3, c3, d8), (a84, b3,c3, d9), (a84, b3, c3, d10), (a84, b3, c3, d11), (a84, b3, c3, d12),(a84, b3, c3, d13), (a84, b3, c3, d14), (a84, b3, c3, d15), (a84, b3,c3, d16), (a84, b3, c3, d17), (a84, b3, c3, d18), (a84, b3, c3, d19),(a84, b3, c3, d20), (a84, b3, c3, d21), (a84, b3, c3, d22), (a84, b4,c1, d1), (a84, b4, c1, d2), (a84, b4, c1, d3), (a84, b4, c1, d4), (a84,b4, c1, d5), (a84, b4, c1, d6), (a84, b4, c1, d7), (a84, b4, c1, d8),(a84, b4, c1, d9), (a84, b4, c1, d10), (a84, b4, c1, d11), (a84, b4, c1,d12), (a84, b4, c1, d13), (a84, b4, c1, d14), (a84, b4, c1, d15), (a84,b4, c1, d16), (a84, b4, b4, d17), (a84, b4, c1, d18), (a84, b4, c1,d19), (a84, b4, c1, d20), (a84, b4, c1, d21), (a84, b4, c1, d22), (a84,b4, c2, d1), (a84, b4, c2, d2), (a84, b4, c2, d3), (a84, b4, c2, d4),(a84, b4, c2, d5), (a84, b4, c2, d6), (a84, b4, c2, d7), (a84, b4, c2,d8), (a84, b4, c2, d9), (a84, b4, c2, d10), (a84, b4, c2, d11), (a84,b4, c2, d12), (a84, b4, c2, d13), (a84, b4, c2, d14), (a84, b4, c2,d15), (a84, b4, c2, d16), (a84, b4, c2, d17), (a84, b4, c2, d18), (a84,b4, c2, d19), (a84, b4, c2, d20), (a84, b4, c2, d21), (a84, b4, c2,d22), (a84, b4, c3, d1), (a84, b4, c3, d2), (a84, b4, c3, d3), (a84, b4,c3, d4), (a84, b4, c3, d5), (a84, b4, c3, d6), (a84, b4, c3, d7), (a84,b4, c3, d8), (a84, b4, c3, d9), (a84, b4, c3, d10), (a84, b4, c3, d11),(a84, b4, c3, d12), (a84, b4, c3, d13), (a84, b4, c3, d14), (a84, b4,c3, d15), (a84, b4, c3, d16), (a84, b4, c3, d17), (a84, b4, c3, d18),(a84, b4, c3, d19), (a84, b4, c3, d20), (a84, b4, c3, d21), (a84, b4,c3, d22), (a84, b5, c1, d1), (a84, b5, c1, d2), (a84, b5, c1, d3), (a84,b5, c1, d4), (a84, b5, c1, d5), (a84, b5, c1, d6), (a84, b5, c1, d7),(a84, b5, c1, d8), (a84, b5, c1, d9), (a84, b5, c1, d10), (a84, b5, c1,d11), (a84, b5, c1, d12), (a84, b5, c1, d13), (a84, b5, c1, d14), (a84,b5, c1, d15), (a84, b5, c1, d16), (a84, b5, c1, d17), (a84, b5, c1,d18), (a84, b5, c1, d19), (a84, b5, c1, d20), (a84, b5, c1, d21), (a84,b5, c1, d22), (a84, b5, c2, d1), (a84, b5, c2, d2), (a84, b5, c2, d3),(a84, b5, c2, d4), (a84, b5, c2, d5), (a84, b5, c2, d6), (a84, b5, c2,d7), (a84, b5, c2, d8), (a84, b5, c2, d9), (a84, b5, c2, d10), (a84, b5,c2, d11), (a84, b5, c2, d12), (a84, b5, c2, d13), (a84, b5, c2, d14),(a84, b5, c2, d15), (a84, b5, c2, d16), (a84, b5, c2, d17) (a84, b5, c2,d18), (a84, b5, c2, d19), (a84, b5, c1, d20), (a84, b5, c1, d21), (a84,b5, c1, d22), (a84, b5, c3, d1), (a84, b5, c3, d2), (a84, b5, c3, d3),(a84, b5, c3, d4), (a84, b5, c3, d5), (a84, b5, c3, d6), (a84, b5, c3,d7), (a84, b5, c3, d8), (a84, b5, c3, d9), (a84, b5, c3, d10), (a84, b5,c3, d11), (a84, b5, c3, d12), (a84, b5, c3, d13), (a84, b5, c3, d14),(a84, b5, c3, d15), (a84, b5, c3, d16), (a84, b5, c3, d17), (a84, b5,c3, d18), (a84, b5, c3, d19), (a84, b5, c3, d20), (a84, b5, c3, d21),(a84, b5, c3, d22), (a84, b6, c1, d1), (a84, b6, c1, d2), (a84, b6, c1,d3), (a84, b6, c1, d4), (a84, b6, c1, d5), (a84, b6, c1, d6), (a84, b6,c1, d7), (a84, b6, c1, d8), (a84, b6, c1, d9), (a84, b6, c1, d10), (a84,b6, c1, d11), (a84, b6, c1, d12), (a84, b6, c1, d13), (a84, b6, c1,d14), (a84, b6, c1, d15), (a84, b6, c1, d16), (a84, b6, c1, d17), (a84,b6, c1, d18), (a84, b6, c1, d19), (a84, b6, c1, d20), (a84, b6, c1,d21), (a84, b6, c1, d22), (a84, b6, c2, d1), (a84, b6, c2, d2), (a84,b6, c2, d3), (a84, b6, c2, d4), (a84, b6, c2, d5), (a84, b6, c2, d6),(a84, b6, c2, d7), (a84, b6, c2, d8), (a84, b1, c2, d9), (a84, b6, c2,d10), (a84, b6, c2, d11), (a84, b6, c2, d12), (a84, b6, c2, d13), (a84,b6, c2, d14), (a84, b6, c2, d15), (a84, b6, c2, d16), (a84, b6, c2,d17), (a84, b6, c2, d18), (a84, b6, c2, d19), (a84, b6, c2, d20), (a84,b6, c2, d21), (a84, b6, c2, d22), (a84, b6, c3, d1), (a84, b6, c3, d2),(a84, b6, c3, d3), (a84, b6, c3, d4), (a84, bb, c3, d5), (a84, bb, c3,d6), (a84, b6, c3, d7), (a84, b6, c3, d8), (a84, b6, c3, d9), (a84, b6,c3, d10), (a84, b6, c3, d11), (a84, b6, c3, d12), (a84, b6, c3, d13),(a84, b6, c3, d14), (a84, b6, c3, d15), (a84, b6, c3, d16), (a84, b6,c3, d17), (a84, b6, c3, d18), (a84, b6, c3, d19), (a84, b6, c3, d20),(a84, b6, c3, d21), (a84, b6, c3, d22), (a85, b1, c1, d1), (a85, b1, c1,d2), (a85, b1, c1, d3), (a85, b1, c1, d4), (a85, b1, c1, d5), (a85, b1,c1, d6), (a85, b1, c1, d7), (a85, b1, c1, d8), (a85, b1, c1, d9), (a85,b1, c1, d10), (a85, b1, c1, d11), (a85, b1, c1, d12), (a85, b1, c1,d13), (a85, b1, c1, d14), (a85, b1, c1, d15), (a85, b1, c1, d16), (a85,b1, c1, d17), (a85, b1, c1, d18), (a85, b1, c1, d19), (a85, b1, c1,d20), (a85, b1, b1, d21), (a85, b1, c1, d22), (a85, b1, c2, d1), (a85,b1, c2, d2), (a85, b1, c2, d3), (a85, b1, c2, d4), (a85, b1, c2, d5),(a85, b1, c2, d6), (a85, b1, c2, d7), (a85, b1, c2, d8), (a85, b1, c2,d9), (a85, b1, c2, d10), (a85, b1, c2, d11), (a85, b1, c2, d12), (a85,b1, c2, d13), (a85, b1, c2, d14), (a85, b1, c2, d15), (a85, b1, c2,d16), (a85, b1, c2, d17), (a85, b1, c2, d18), (a85, b1, c2, d19), (a85,b1, c2, d20), (a85, b1, c2, d21), (a85, b1, c2, d22), (a85, b1, c3, d1),(a85, b1, c3, d2), (a85, b1, c3, d3), (a85, b1, c3, d4), (a85, b1, c3,d5), (a85, b1, c3, d6), (a85, b1, c3, d7), (a85, b1, c3, d8), (a85, b1,c3, d9), (a85, b1, c3, d10), (a85, b1, c3, d11), (a85, b1, c3, d12),(a85, b1, c3, d13), (a85, b1, c3, d14), (a85, b1, c3, d15), (a85, b1,c3, d16), (a85, b1, c3, d17), (a85, b1, c3, d18), (a85, b1, c3, d19),(a85, b1, c3, d20), (a85, b1, c3, d21), (a85, b1, c3, d22), (a85, b2,c1, d1), (a85, b2, c1, d2), (a85, b2, c1, d3), (a85, b2, c1, d4), (a85,b2, c1, d5), (a85, b2, c1, d6), (a85, b2, c1, d7), (a85, b2, c1, d8),(a85, b2, c1, d9), (a85, b2, c1, d10), (a35, b2, c1, d11), (a85, b2, c1,d12), (a85, b2, c1, d13), (a85, b2, c1, d14), (a85, b2, c1, d15), (a85,b2, c1, d16), (a85, b2, c1, d17), (a85, b2, c1, d18), (a85, b2, c1,d19), (a85, b2, c1, d20), (a85, b2, c1, d21), (a85, b2, c1, d22), (a85,b2, c2, d1), (a85, b2, c2, d2), (a85, b2, c2, d3), (a85, b2, c2, d4),(a85, b2, c2, d4), (a85, b2, c2, d7), (a85, b2, c2, d8), (a85, b2, c2,d9), (a85, b2, c2, d10), (a85, b2, c2, d11), (a85, b2, c2, d12), (a85,b2, c2, d13), (a85, b2, c2, d14), (a85, b2, c2, d16), (a85, b2, c2,d16), (a85, b2, c2, d17), (a85, b2, c2, d18), (a85, b2, c2, d19), (a85,b2, c2, d20), (a85, b2, c2, d21), (a85, b2, c2, d22), (a85, b2, c3, d1),(a85, b2, c3, d2), (a85, b2, c3, d3), (a85, b2, c3, d14), (a85, b2, c3,d5), (a85, b2, c3, d6), (a85, b2, c3, d7), (a85, b2, c3, d8), (a85, b2,c3, d9), (a83, b2, c3, d10), (a85, b2, c3, d11), (a85, b2, c3, d12),(a85, b2, c3, d13), (a85, b2, c3, d14), (a85, b2, c3, d15), (a85, b2,c3, d16), (a85, b2, c3, d17), (a85, b2, c3, d18), (a85, b2, c3, d19),(a85, b2, c3, d20), (a85, b2, c3, d21), (a85, b2, c3, d22), (a85, b3,c1, d1), (a85, b3, c1, d2), (a85, b3, c1, d3), (a85, b2, c1, d4), (a85,b3, c1, d5), (a85, b3, c1, d6), (a85, b3, c1, d7), (a85, b3, c1, d5),(a85, b3, c1, d9), (a85, b3, c1, d10), (a85, b3, c1, d11), (a85, b3, c1,d12), (a35, b3, c1, d13), (a85, b3, c1, d14), (a85, b3, c1, d15), (a85,b3, c1, d16), (a85, b3, c1, d17), (a85, b3, c1, d18), (a85, b3, c1,d19), (a83, b3, c1, d20), (a85, b3, c1, d21), (a35, b3, c1, d22), (a85,b3, c2, d1), (a85, b3, c2, d2), (a85, b3, c2, d3), (a85, b5, c2, d4),(a85, b3, c2, d5), (a85, b3, c2, d6), (a85, b3, c2, d7), (a85, b3, c2,d8), (a85, b3, c2, d9), (a85, b3, c2, d10), (a85, b3, c2, d11), (a85,b3, c2, d12), (a85, b3, c2, d13), (a85, b3, c2, d14), (a85, b3, c2,d15), (a85, b3, c2, d16), (a85, b3, c2, d17), (a85, b3, c2, d18), (a85,b3, c2, d19), (a85, b3, c2, d20), (a85, b3, c2, d21), (a85, b3, c2,d22), (a85, b3, c3, d1), (a85, b3, c3, d2), (a85, b3, c3, d3), (a85, b3,c3, d4), (a85, b3, c3, d5), (a85, b3, c3, d6), (a85, b3, c3, d7), (a83,b3, c3, d8), (a85, b3, c3, d9), (a85, b3, c3, d10), (a85, b3, c3, d11),(a85, b3, c3, d12), (a85, b3, c3, d13), (a85, b3, c3, d14), (a85, b3,c3, d15), (a85, b3, c3, d16), (a85, b3, c3, d17), (a85, b3, c3, d18),(a85, b3, c3, d18), 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d5), (a85, b4, c3, d6), (a85, b4,c3, d7), (a85, b4, c3, d8), (a85, b4, c3, d9), (a85, b4, c3, d10), (a85,b4, c3, d11), (a85, b4, c3, d12), (a85, b4, c3, d13), (a85, b4, c3,d14), (a85, b4, c3, d15), (a85, b4, c3, d16), (a85, b4, c3, d17), (a85,b4, c3, d18), (a85, b4, c3, d19), (a85, b4, c3, d20), (a85, b4, c3,d21), (a85, b4, c3, d22), (a85, b5, c1, d), (a85, b5, c1, d2), (a85, b5,c1, d3), (a85, b5, c1, d4), (a85, b5, c1, d5), (a85, b5, c1, d6), (a85,b5, c1, d7), (a85, b5, c1, d8), (a85, b5, c1, d9), (a85, b5, c1, d10),(a85, b5, c1, d11), (a85, b5, c1, d12), (a83, b5, c1, d13), (a85, b5,c1, d14), (a85, b5, c1, d15), (a85, b5, c1, d16), (a85, b5, c1, d17),(a85, b5, c1, d18), (a85, b5, c1, d9), (a85, b5, c1, d20), (a85, b5, c1,d21), (a85, b5, c1, d22), (a85, b5, c2, d1), (a85, b5, c2, d2), (a85,b5, c2, d3), (a85, b5, c2, d4), (a85, b5, c2, d5), (a85), (a85, c2, d6),(a85, b5, c2, d7), (a85, b5, c2, d8), (a85, b5, c2, d9), (a85, b5, c2,d10), (a85, b5, c2, d11), (a85, b5, c2, d12), (a85, b5, 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(a86,b5, c1, d1), (a86, b5, c1, d2), (a86, b5, c1, d3), (a86, b5, c1, d4),(a6, b5, c1, d5), (a86, b5, c1, d6), (a86, b5, c1, d7), (a86, b5, c1,d8), (a86, b5, c1, d9), (a86, b5, c1, d10), (a86, b5, c1, d11), (a86,b5, c1, d12), (a86, b5, c1, d13), (a86, b5, c1, d14), (a86, b5, c1,d15), (a86, b5, c1, d16), (a86, b5, c1, d17), (a86, b5, c1, d18), (a86,b5, c1, d19), (a86, b5, c1, d20), (a86, b5, c1, d21), (a86, b5, c1,d22), (a86, b5, c2, d1), (a86, b5, c2, d2), (a86, b5, c2, d3), (a86, b5,c2, d4), (a86, b5, c2, d5), (a86, b5, c2, d6), (a86, b5, c2, d7), (a86,b5, c2, d8), (a86, b5, c2, d9), (a86, b5, c2, d10), (a36, b5, c2, d11),(a86, b5, c2, d12), (a86, b5, c2, d13), (a86, b5, c2, d14), (a86, b5,c2, d15), (a86, b5, c2, d16), (a86, b5, c2, d17), (a86, b5, c2, d18),(a86, b5, c2, d19), (a36, b5, c2, d20), (a86, b5, c2, d21), (a86, b5,c2, d22), (a86, b5, c3, d1), (a86, b5, c3, d2), (a86, b5, c3, d3), (a86,b5, c3, d4), (a86, b5, c3, d5), (a86, b5, c3, d6), (a86, b5, c3, d7),(a86, b5, c3, d8, 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d16), (a86, b6, c2, d17), (a86, b6,c2, d18), (a86, b6, c2, d19), (a86, b6, c2, d20), (a86, b6, c2, d21),(a86, b6, c2, d22), (a86, b6, c3, d1), (a86, b6, c3, d2), (a86, b6, c3,d3), (a86, b6, c3, d4), (a86, b6, c3, d5), (a86, b6, c3, d6), (a86, b6,c3, d6), (a86, b6, c3, d8), (a86, b6, c3, d9), (a86, b6, c3, d10), (a86,b6, c3, d11), (a86, b6, c3, d12), (a86, b6, c3, d13), (a86, b6, c3,d14), (a86, b6, c3, d15), (a86, b6, c3, d16), (a86, b6, c3, d17), (a86,b6, c3, d18), (a86, b6, c3, d19), (a86, b6, c3, d20), (a86, b6, c3,d21), (a86, b6, c3, d22), (a87, b1, c1, d1), (a87, b1, c1, d2), (a87,b1, c1, d3) (a57, b1, c1, d4), (a87, b1, c1, d5), (a87, b1, c1, d6),(a87, b1, c1, d7), (a87, b1, c1, d8), (a87, b1, c1, d9), (a87, b1, c1,d10), (a87, b1, c1, d11), (a87, b1, c1, d12), (a87, b1, c1, d13), (a87,b1, c1, d14), (a87, b1, c1, d15), (a87, b1, c1, d16), (a87, b1, c1,d17), (a87, b1, c1, d18), (a87, b1, c1, d19), (a87, b1, c1, d20), (a87,b1, c1, d21), (a87, b1, c1, d22), (a87, b1, c2, d1), (a87, b1, c2, d2),(a87, b1, c2, d3), (a87, b1, c2, d4), (a87, b1, c2, d5), (a87, b1, c2,d6), (a87, b1, c1, d7), (a87, b1, c2, d8), (a87, b1, c2, d9), (a87, b1,c2, d10), (a87, b1, c2, d11), (a87, b1, c2, d12), (a87, b1, c2, d13),(a87, b1, c2, d14), (a87, b1, c2, d15), (a87, b1, c2, d16), (a87, b1,c2, d17), (a87, b1, c2, d18), (a87, b1, c2, d19), (a87, b1, c1, d20),(a87, b1, c2, d21), (a87, b1, c2, d22), (a87, b1, c3, d1), (a87, b1, c3,d2), (a87, b1, c3, d3), (a87, b1, c3, d4), (a87, b1, c3, d5), (a87, b1,c3, d6), (a87, b1, c3, d7), (a87, b1, c3, d8), (a87, b1, c3, d9), (a87,b1, c3, d10), (a87, b1, c3, d11), (a87, b1, c3, d12), (a87, b1, c3,d13), (a87, b1, c3, d14), (a87, b1, c3, d15), (a87, b1, c3, d16), (a87,b1, c3, d17), (a87, b1, c3, d18), (a87, b1, c3, d19), (a87, b1, c3,d20), (a87, b1, c3, d21), (a87, b1, c3, d22), (a87, b2, c1, d1), (a87,b2, c1, d2), (a87, b2, c1, d3), (a87, b2, c1, d4), (a87, b2, c1, d5),(a87, b2, c1, d6), (a87, b2, c1, d7), (a87, b2, c1, d8), (a87, b2, c1,d9), (a87, b2, c1, d10), (a87, b2, c1, d11), (a87, b2, c1, d12), (a87,b2, c1, d13), (a87, b2, c1, d14), (a87, b2, c1, d15), (a87, b2, c1,d16), (a87, b2, c1, d17), (a87, b2, c1, d18), (a87, b2, c1, d19), (a87,b2, c1, d20), (a87, b2, c1, d21), (a87, b2, c1, d22), (a87, b2, c2, d1),(a87, b2, c2, d2), (a87, b2, c2, d3), (a87, b2, c2, d4), (a87, b2, c2,d5), (a87, b2, c2, d6), (a87, b2, c2, d7), (a87, b2, c2, d8), (a87, b2,c2, d9), (a87, b2, c2, d10), (a87, b2, c2, d11), (a87, b2, c2, d12),(a87, b2, c2, d13), (a87, b2, c2, d14), (a87, b2, c2, d15), (a87, b2,c2, d16), (a87, b2, c2, d17), (a87, b2, c2, d18), (a87, b2, c2, d19),(a87, b2, c2, d20), (a87, b2, c2, d21), (a87, b2, c2, d22), (a87, b2,c3, d1), (a87, b2, c3, d2), (a87, b2, c3, d3), (a87, b2, c3, d4), (a87,b2, c3, d5), (a87, b2, c3, d6), (a87, b2, c3, d7), (a87, b2, c3, d8),(a87, b2, c3, d9), (a87, b2, c3, d10), (a87, b2, c3, d11), (a87, b2, c3,d12), (a87, b2, c3, d13), (a87, b2, c3, d14), (a87, b2, c3, d15), (a37,b2, c3, d16), (a87, b2, c3, d17), (a87, b2, c3, d18), (a87, b2, c3,d19), (a87, b2, c3, d20), (a87, b2, c3, d21), (a87, b2, c3, d22), (a87,b3, c1, d1), (a87, b3, c1, d2), (a87, b3, c1, d3), (a87, b3, c1, d4),(a87, b3, c1, d5), (a87, b3, c1, d6), (a87, b3, c1, d7), (a87, b3, c1,d8), (a87, b3, c1, d9), (a87, b3, c1, d10), (a87, b3, c1, d11), (a87,b3, c1, d12), (a87, b3, c1, d13), (a87, b3, c1, d14), (a87, b3, c1,d15), (a87, b3, c1, d16), (a87, b3, c1, d17), (a87, b3, c1, d18), (a87,b3, c1, d19), (a87, b3, c1, d20), (a87, b3, c1, d21), (a87, b3, c1,d22), (a87, b3, c2, d1), (a87, b3, c2, d2), (a87, b3, c2, d3), (a87, b3,c2, d4), (a87, b3, c2, d5), (a87, b3, c2, d6), (a87, b3, c2, d7), (a87,b3, c2, d8), (a87, b3, c2, d9), (a87, b3, c2, d10), (a87, b3, c2, d11),(a87, b3, c2, d12), (a87, b3, c2, d13), (a87, b3, c2, d14), (a87, b3,c2, d15), (a87, b3, c2, d16), (a87, b3, c2, d17), (a87, b5, c2, d18),(a87, b3, c2, d19), (a87, b3, c2, d20), (a87, b3, c2, d21), (a87, b3,c2, d22), (a87, b3, c3, d1), (a87, b3, c3, d2), (a87, b3, c3, d3), (a87,b3, c3, d4), (a87, b3, c3, d5), (a87, b3, c3, d6), (a87, b3, c3, d7),(a87, b3, c3, d8), (a87, b3, c3, d9), (a87, b3, c3, d10), (a87, b3, c3,d11), (a87, b3, c3, d12), (a87, b3, c3, d13), (a37, b3, c3, d14), (a37,b3, c3, d15), (a87, b3, c3, d16), (a87, b3, c3, d17), (a87, b3, c3,d18), (a87, b3, c3, d19), (a87, b3, c3, d20), (a87, b3, c3, d21), (a87,b3, c3, d22), (a87, b4, c1, d1), (a7, b4, c1, d12), (a87, b4, c1, d3),(a87, b4, c1, d4), (a87, b4, c1, d5), (a87, b4, c1, d6), (a87, b4, c1,d7), (a87, b4, c1, d8), (a87, b4, c1, d9), (a87, b4, c1, d10), (a87, b4,c1, d11), (a87, b4, c1, d12), (a87, b4, c1, d13), (a87, b4, c1, d14),(a87, b4, c1, d15), (a87, b4, c1, d16), (a87, b4, c1, d17), (a87, b4,c1, d18), (a87, b4, c1, d19), (a87, b4, c1, d20), (a87, b4, c1, d21),(a87, b4, c1, d22), (a87, b4, c2, d1), (a87, b4, c2, d2), (a87, b4, c2,d3), (a87, b4, c2, d4), (a87, b4, c2, d5), (a37, b4, c2, d6), (a87, b4,c2, d7), (a87, b4, c2, d8), (a87, b4, c2, d9), (a87, b4, c2, d10), (a87,b4, c2, d11), (a87, b4, c2, d12), (a87, b4, c2, d13), (a87, b4, c2,d14), (a87, b4, c2, d15), (a87, b4, c2, d16), (a87, b4, c2, d17), (a87,b4, c2, d18), (a87, b4, c2, d19), (a87, b4, c2, d20), (a87, b4, c2,d21), (a87, b4, c2, d22), (a87, b4, c3, d1), (a87, b4, c3, d2), (a87,b4, c3, d3), (a87, b4, c3, d14), (a87, b4, c3, d5), (a87, b4, c3, d6),(a87 b4, c3, d7), (a87, b4, c3, d8), (a87, b4, c3, d9), (a87, b4, c3,d10), (a87, b4, c3, d11), (a87, b4, c3, d12), (a87, b4, c3, d13), (a87,b4, c3, d14), (a87, b4, c3, d15), (a87, b4, c3, d16), (a87, b4, c3,d17), (a87, b4, c3, d15), (a87, b4, c3, d19), (a87, b4, c3, d20), (a87,b4, c3, d21), (a87, b4, c3, d22), (a87, b5, c1, d1), (a87, b5, c1, d2),(a87, b5, c1, d3), (a87, b5, c1, d4), (a87, b5, c1, d5), (a37, b5, c1,d6), (a87, b5, c1, d7), (a87, b5, c1, d8), (a37, b5, c1, d9), (a87, b5,c1, d10), (a87, b5, c1, d11), (a87, b5, c1, d12), (a37, b5, c1, d13),(a87, b5, c1, d14), (a87, b5, c1, d15), (a87, b5, c1, d16), (a87, b5,c1, d17), (a37, b5, c1, d18), (a87, b5, c1, d19), (a87, b5, c1, d20),(a87, b5, c1, d21), (a87, b5, c1, d22), (a87, b5, c2, d1), (a87, b5, c2,d2), (a87, b5, c2, d3), (a87, b5, c2, d4), (a87, b5, c2, d5), (a87, b5,c2, d6), (a87, b5, c2, d7), (a87, b5, c2, d8), (a87, b5, c2, d9), (a87,b5, c2, d10), (a87, b5, c2, d11), (a87, b5, c2, d12), (a87, b5, c2,d13), (a87, b5, c2, d14), (a87, b5, c2, d15), (a87, b5, c2, d16), (a87,b5, c2, d17), (a87, b5, c2, d18), (a87, b5, c2, d19), (a87, b5, c2,d20), (a87, b5, c2, d21), (a87, b5, c2, d22), (a87, b5, c3, d1), (a87,b5, c3, d2), (a87, b5, c3, d3), (a87, b5, c3, d4), (a87, b5, c3, d5),(a87, b5, c3, d6), (a37, b5, c3, d7), (a87, b5, c3, d8), (a87, b5, c3,d9), (a87, b5, c3, d10), (a87, b5, c3, d11), (a87, b5, c3, d12, (a87,b5, c3, d13), (a87, b5, c3, d14), (a87, b5, c3, d15), (a87, b5, c3,d16), (a87, b5, c3, d17), (a87, b5, c3, d18), (a87, b5, c3, d19), (a87,b5, c3, d20), (a87, b5, c3, d21), (a87, b5, c3, d22), (a87, b6, c1, d1),(a87, b6, c1, d2), (a87, b6, c1, d3), (a87, b6, c1, d4), (a87, b6, c1,d5), (a87, b6, c1, d6), (a87, b6, c1, d7), (a87, b6, c1, d8), (a87, b6,c1, d9), (a87, b6, c1, d10), (a87, b6, c1, d11), (a87, b6, c1, d12),(a87, b6, c1, d13), (a87, b6, c1, d14), (a87, b6, c1, d15), (a87, b6,c1, d16), (a87, b6, c1, d17), (a87, b6, c1, d18), (a87, b6, c1, d19),(a87, b6, c1, d20), (a87, b6, c1, d21), (a87, b6, c1, d22), (a87, b6,c2, d1), (a87, b6, c2, d2), (a87, b6, c2, d3), (a87, b6, c2, d4), (a87,b6, c2, d5), (a87, b6, c2, d6), (a87, b6, c2, d7), (a87, b6, c2, d8),(a87, b6, c2, d9), (a87, b6, c2, d10), (a87, b6, c2, d11), (a87, b6, c2,d12), (a87, b6, c2, d13), (a87, b6, c2, d14), (a87, b6, c2, d15), (a87,b6, c2, d16), (a87, b6, c2, d17), (a87, b6, c2, d18), (a87, b6, c2,d19), (a37, b6, c2, d20), (a87, b6, c2, d21), (a87, b6, c2, d22), (a87,b6, c3, d1), (a87, b6, c3, d2), (a87, b6, c3, d3), (a87, b6, c3, d4),(a87, b6, c3, d5), (a87, b6, c3, d6), (a87, b6, c3, d7), (a87, b6, c3,d8), (a87, b6, c3, d9), (a87, b6, c3, d10), (a87, b6, c3, d11), (a87,b6, c3, d12), (a87, b6, c3, d13), (a87, b6, c3, d14), (a87, b6, c3,d15), (a87, b6, c3, d16), (a87, b6, c3, d17), (a87, b6, c3, d18), (a87,b6, c3, d19), (a87, b6, c3, d20), (a87, b6, c3, d21), (a87, b6, c3,d22), (a88, b1, c1, d1), (a88, b1, c1, d2), (a88, b1, c1, d3), (a88, b1,c1, d4), (a88, b1, c1, d5), (a38, b1, c1, d6), (a88, b1, c1, d7), (a88,b1, c1, d8), (a88, b1, c1, d9), (a88, b, c1, d10), (a88, b1, c1, d11),(a88, b1, c1, d12), (a88, b1, c1, d13), (a88, b1, c1, d14), (a88, b1,c1, d15), (a88, b1, c1, d16), (a88, b1, c1, d17), (a88, b1, c1, d18),(a88, b1, c1, d19), (a88, b1, c1, d20), (a88, b1, c1, d21), (a88, b, c1,d22), (a88, b1, c2, d1), (a88, b1, c2, d2), (a88, b1, c2, d3), (a88, b1,c2, d4), (a88, b1, c2, d5), (a88, b1, c2, d6), (a88, b1, c2, d7), (a88,b1, c2, d8), (a88, b1, c2, d9), (a88, b1, c2, d10), (a88, b1, c2, d11),(a88, b1, c2, d12), (a88, b1, c2, d13), (a88, b1, c2, d14), (a88, b1,c2, d15), (a88, b1, c2, d16), (a88, b1, c2, d17), (a88, b1, c2, d18),(a88, b1, c2, d19), (a88, b1, c2, d20), (a88, b1, c2, d21), (a88, b1,c2, d22), (a88, b1, c3, d1), (a88, b1, c3, d2), (a88, b1, c3, d3), (a88,b1, c3, d4), (a88, b1, c3, d5), (a88, b1, c3, d6), (a88, b1, c3, d7),(a88, b1, c3, d8), (a88, b1, c3, d9), (a88, b1, c3, d10), (a88, b1, c3,d11), (a88, b1, c3, d12), (a8, b1, c3, d13), (a88, b1, c3, d14), (a88,b1, c3, d15), (a88, b1, c3, d16), (a88, b1, c3, d17), (a88, b1, c3,d18), (a88, b1, c3, d19), (a88, b1, c3, d20), (a88, b1, c3, d21), (a88,b1, c3, d22), (a88, b2, c1, d1), (a88, b2, c1, d2), (a88, b2, c1, d3),(a88, b2, c1, d4), (a88, b2, c1, d5), (a88, b2, c1, d6), (a88, b2, c1,d7), (a88, b2, c1, d8), (a88, b2, c1, d9), (a88, b2, c1, d10), (a88, b2,c1, d11), (a88, b2, c1, d12), (a88, b2, c1, d13), (a88, b2, c1, d14),(a88, b2, c1, d15), (a88, b2, c1, d16), (a88, b2, c3, d17), (a88, b2,c1, d18), (a88, b2, c1, d19), (a88, b2, c1, d20), (a88, b2, c1, d21),(a88, b2, c1, d22), (a88, b2, c2, d1), (a88, b2, c2, d2), (a88, b2, c2,d3), (a88, b2, c2, d4), (a88, b2, c2, d5), (a88, b2, c2, d6), (a88, b2,c2, d7), (a88, b2, c2, d8), (a88, b2, c2, d9), (a88, b2, c2, d10), (a88,b2, c2, d11), (a88, b2, c2, d12), (a88, b2, c2, d13), (a88, b2, c2,d14), (a88, b2, c2, d15), (a88, b2, c2, d16), (a88, b2, c2, d17), (a88,b2, c2, d18), (a88, b2, c2, d19), (a88, b2, c2, d20), (a88, b2, c2,d21), (a88, b2, c2, d22), (a88, b2, c3, d1), (a88, b2, c3, d2), (a88,b2, c3, d3), (a88, b2, c3, d4), (a88, b2, c3, d5), (a88, b2, c3, d6),(a88, b2, c1, d7), (a88, b2, c3, d8), (a88, b2, c3, d9), (a88, b2, c3,d10), (a88, b2, c3, d11), (a88, b2, c3, d12), (a88, b2, c3, d13), (a88,b2, c3, d14), (a88, b2, c3, d15), (a88, b2, c3, d16), (a88, b2, c3,d17), (a88, b2, c3, d18), (a88, b2, c3, d19), (a88, b2, c3, d20), (a88,b2, c3, d21), (a88, b2, c3, d22), (a88, b3, c1, d1), (a88, b3, c1, d2),(a88, b3, c1, d3), (a88, b3, c1, d4), (a88, b3, c1, d5), (a38, b3, c1,d6), (a88, b3, c1, d7), (a88, b3, c1, d8), (a88, b3, c1, d9), (a88, b3,c1, d10), (a88, b3, c1, d11), (a88, b3, c1, d12), (a88, b3, c1, d13),(a88, b3, c1, d14), (a88, b3, c1, d15), (a88, b3, c1, d16), (a88, b3,c1, d17), (a88, b3, c1, d18), (a88, b3, c1, d19), (a88, b3, c1, d20),(a88, b3, c1, d21), (a88, b3, c1, d22), (a88, b3, c2, d1), (a88, b3, c2,d2), (a88, b3, c2, d3), (a88, b3, c2, d4), (a88, b3, c2, d5), (a88, b3,c2, d6), (a88, b3, c2, d7), (a88, b3, c2, d8), (a88, b3, c2, d9), (a88,b3, c2, d10), (a88, b3, c2, d11), (a88, b3, c2, d12), (a38, b3, c2,d13), (a88, b3, c2, d14), (a88, b3, c2, d15), (a88, b3, c2, d16), (a88,b3, c2, d17), (a88, b3, c2, d18), (a88, b3, c2, d19), (a88, b3, c2,d20), (a88, b3, c2, d21), (a88, b3, c2, d22), (a88, b3, c3, d1), (a88,b3, c3, d2), (a88, b3, c3, d3), (a88, b3, c3, d4), (a88, b3, c3, d5),(a88, b3, c3, d6), (a88, b3, c3, d7), (a88, b3, c3, d8), (a88, b3, c3,d9), (a88, b3, c3, d10), (a88, b3, c3, d11), (a88, b3, c3, d12), (a88,b3, c3, d13), (a88, b3, c3, d14), (a88, b3, c3, d15), (a88, b3, c3,d16), (a88, b3, c3, d17), (a88, b3, c3, d18), (a88, b3, c3, d19), (a88,b3, c3, d20), (a88, b3, c3, d21), (a88, b3, c3, d22), (a88, b4, c1, d1),(a88, b4, c1, d2), (a88, b4, c1, d3), (a88, b4, c1, d4), (a88, b4, c1,d5), (a88, b4, c1, d6), (a88, b4, c1, d7), (a88, b4, c1, d8), (a88, b4,c1, d9), (a38, b4, c1, d10), (a88, b4, c1, d11), (a88, b4, c1, d12),(a88, b4, c1, d13), (a88, b4, c1, d14), (a88, b4, c1, d15), (a88, b4,c1, d16), (a88, b4, c1, d17), (a88, b4, c1, d18), (a88, b4, c1, d19),(a88, b4, c1, d20), (a88, b4, c1, d21), (a88, b4, c1, d22), (a88, b4,c2, d1) (a88, b4, c2, d2), (a88, b4, c2, d5), (a88, b4, c2, d4), (a88,b4, c2, d5), (a88, b4, c2, d6), (a88, b4, c2, d7), (a88, b4, c2, d8),(a88, b4, c2, d9), (a88, b4, c2, d10), (a88, b4, c2, d11), (a88, b4, c2,d12), (a88, b4, c2, d13), (a88, b4, c2, d14), (a88, b4, c2, d15), (a88,b4, c2, d16), (a88, b4, c2, d17), (a88, b4, c2, d18), (a88, b4, c2,d19), (a88, b4, c2, d20), (a88, b4, c2, d21), (a88, b4, c2, d22), (a88,b4, c3, d1), (a88, b4, c3, d2), (a88, b4, c3, d3), (a88, b4, c3, d4),(a88, b4, c3, d5), (a88, b4, c3, d6), (a88, b4, c3, d7), (a88, b4, c3,d8), (a88, b4, c3, d9), (a88, b4, c3, d10), (a88, b4, c3, d11), (a88,b4, c3, d12), (a88, b4, c3, d13), (a88, b4, c3, d14), (a88, b4, c3,d15), (a88, b4, c3, d16), (a88, b4, c3, d17), (a88, b4, c3, d18), (a88,b4, c3, d19), (a88, b4, c3, d20), (a88, b4, c3, d21), (a88, b4, c3,d22), (a88, b5, c1, d1), (a88, b5, c1, d2), (a88, b5, c1, d3), (a88, b5,c1, d4), (a88, b5, c1, d5), (a88, b5, c1, d6), (a88, b5, c1, d7), (a88,b5, c1, d8), (a88, b5, c1, d9), (a88, b5, c1, d10), (a88, b5, c1, d11),(a88, b5, c1, d12), (a88, b5, c1, d13), (a88, b5, c1, d14), (a88, b5,c1, d15), (a88, b5, c1, d16), (a88, b5, c1, d17), (a88, b5, c1, d18),(a88, b5, c1, d19), (a88, b5, c1, d20), (a88, b5, c1, d21), (a88, b5,c1, d22), (a88, b5, c2, d1), (a88, b5, c2, d2), (a88, b5, c2, d3), (a88,b5, c2, d4), (a88, b5, c2, d5), (a88, b5, c2, d6), (a88, b5, c2, d7),(a88, b5, c2, d8), (a88, b5, c2, d9), (a88, b5, c2, d10), (a88, b5, c2,d11), (a88, b5, c2, d12), (a88, b5, c2, d13), (a88, b5, c2, d14), (a88,b5, c2, d15), (a88, b5, c2, d16), (a88, b5, c2, d17), (a88, b5, c2,d18), (a88, b5, c2, d19), (a88, b5, c2, d20), (a88, b5, c2, d21), (a88,b5, c2, d22), (a88, b5, c3, d1), (a88, b5, c3, d2), (a88, b5, c3, d3),(a88, b5, c3, d4), (a88, b5, c3, d5), (a88, b5, c3, d6), (a88, b5, c3,d7), (a88, b5, c3, d8, (a88, b5, c3, d9), (a88, b5, c3, d10), (a88, b5,c3, d11), (a88, b5, c3, d12), (a88, b5, c3, d13), (a88, b5, c3, d14),(a88, b5, c3, d15), (a88, b5, c3, d16), (a88, b5, c3, d17), (a88, b5,c3, d18), (a88, b5, c3, d19), (a88, b5, c3, d20), (a88, b5, c3, d21),(a88, b5, c3, d22), (a88, b6, c1, d1), (a88, b6, c1, d2), (a88, b6, c1,d3), (a88, b6, c1, d4), (a88, b6, c1, d5), (a88, b6, c1, d6), (a88, b6,c1, d7), (a88, b6, c1, d8), (a88, b6, c1, d9), (a88, b6, c1, d10), (a88,b6, c1, d11), (a88, b6, c1, d12), (a88, b6, c1, d13), (a38, b6, c1,d14), (a88, b6, c1, d15), (a88, b6, c1, d16), (a88, b6, c1, d17), (a88,b6, c1, d18), (a88, b6, c1, d19), (a88, b6, c1, d20), (a88, b6, c1,d21), (a88, b6, c1, d22), (a88, b6, c2, d1), (a88, b6, c2, d2), (a88,b6, c2, d3), (a88, b6, c2, d4), (a88, b6, c2, d5), (a88, b6, c2, d6),(a88, b6, c2, d7), (a88, b6, c2, d8), (a88, b6, c2, d9), (a88, b6, c2,d10), (a88, b6, c2, d11), (a88, b6, c2, d12), (a88, b6, c2, d13), (a88,b6, c2, d14), (a88, b6, c2, d15), (a88, b6, c2, d16), (a88, b6, c2,d17), (a88, b6, c2, d18), (a88, b6, c2, d19), (a88, b6, c2, d20), (a88,b6, c2, d21), (a88, b6, c2, d22), (a88, b6, c3, d1), (a88, b6, c3, d2),(a88, b6, c3, d3), (a88, b6, c3, d4), (a88, b6, c3, d5), (a88, b6, c3,d6), (a88, b6, c3, d7), (a88, b6, c3, d8), (a88, b6, c3, d9), (a88, b6,c3, d10), (a88, b6, c3, d11), (a88, b6, c3, d12), (a88, b6, c3, d13),(a88, b6, c3, d14), (a88, b6, c3, d15), (a88, b6, c3, d16), (a88, b6,c3, d17), (a88, b6, c3, d18), (a88, b6, c3, d19), (a88, b6, c3, d20),(a88, b6, c3, d21), (a88, b6, c3, d22), (a89, b1, c1, d1), (a89, b1, c1,d2), (a89, b1, c1, d3), (a89, b1, c1, d4), (a89, b1, c1, d5), (a89, b1,c1, d6), (a89, b1, c1, d7), (a89, b1, c1, d8), (a89, b1, c1, d9), (a89,b1, c1, d10), (a89, b1, c1, d11), (a89, b1, c1, d12), (a89, b1, c1,d13), (a89, b1, c1, d14), (a89, b1, c1, d15), (a89, b1, c1, d16), (a89,b1, c1, d17), (a89, b1, c1, d18), (a89, b1, c1, d19), (a89, b1, c1,d20), (a89, b1, c1, d21), (a89, b1, c1, d22), (a89, b1, c2, d1), (a89,b1, c2, d2), (a89, b1, c2, d3), (a89, b1, c2, d4), (a89, b1, c2, d5),(a89, b1, c2, d6), (a89, b1, c2, d7), (a89, b1, c2, d8), (a89, b1, c2,d9), (a89, b1, c2, d10), (a89, b1, c2, d11), (a89, b1, c2, d12), (a89,b1, c2, d13), (a89, b1, c2, d14), (a89, b1, c2, d15), (a89, b1, c2,d16), (a89, b1, c2, d17), (a89, b1, c2, d18), (a89, b1, c2, d19), (a89,b1, c2, d20), (a89, b1, c2, d21), (a89, b1, c2, d22), (a89, b1, c3, d1),(a89, b1, c3, d2), (a89, b1, c3, d3), (a89, b1, c3, d4), (a89, b1, c3,d5), (a88, b1, c3, d6), (a89, b1, c3, d7), (a89, b1, c3, d8), (a89, b1,c3, d9), (a89, b1, c3, d10), (a89, b1, c3, d11), (a89, b1, c3, d12),(a89, b1, c3, d13), (a89, b1, c3, d14), (a89, b1, c3, d15), (a89, b1,c3, d16), (a89, b1, c3, d17), (a89, b1, c3, d18), (a89, b1, c3, d19),(a89, b1, c3, d20), (a89, b1, c3, d21), (a89, b1, c3, d22), (a89, b2,c1, d1), (a89, b2, c1, d2), (a89, b2, c1, d5), (a89, b2, c1, d4), (a89,b2, c1, d5), (a89, b2, c1, d6), (a89, b2, c1, d7), (a89, b2, c1, d8),(a89, b2, c1, d9), (a89, b2, c1, d10), (a89, b2, c1, d11), (a89, b2, c1,d12), (a89, b2, c1, d13), (a89, b2, c1, d14), (a89, b2, c1, d15), (a89,b2, c1, d16), (a89, b2, c1, d17), (a89, b2, c1, d18), (a89, b2, c1,d19), (a89, b2, c1, d20), (a89, b2, c1, d21), (a89, b2, c1, d22), (a89,b2, c2, d1), (a89, b2, c2, d2), (a89, b2, c2, d3), (a89, b2, c2, d4),(a89, b2, c2, d5), (a89, b2, c2, d6), (a89, b2, c2, d7), (a89, b2, c2,d8), (a89, b2, c2, d9), (a89, b2, c2, d10), (a89, b2, c2, d11), (a89,b2, c2, d12), (a89, b2, c2, d13), (a89, b2, c2, d14), (a89, b2, c2,d15), (a89, b2, c2, d₁₆), (a89, b2, c2, d17), (a89, b2, c2, d18), (a89,b2, c2, d19), (a89, b2, c2, d20), (a89, b2, c2, d21), (a89, b2, c2,d22), (a89, b2, c3, d1), (a89, b2, c3, d2), (a89, b2, c3, d3), (a89, b2,c3, d4), (a89, b2, c3, d5), (a89, b2, c3, d6), (a89, b2, c3, d7), (a89,b2, c3, d8), (a89, b2, c3, d9), (a89, b2, c3, d10), (a89, b2, c3, d11),(a89, b2, c3, d12), (a89, b2, c3, d13), (a89, b2, c3, d14), (a89, b2,c3, d15), (a89, b2, c3, d16), (a89, b2, c3, d17), (a89, b2, c3, d18),(a89, b2, c3, d19), (a89, b2, c3, d20), (a89, b2, c3, d21), (a89, b2,c3, d22), (a89, b3, c1, d1), (a89, b3, c1, d2), (a89, b3, c1, d3), (a89,b3, c1, d4), (a89, b3, c1, d5), (a89, b3, c1, d6), (a89, b3, c1, d7),(a89, b3, c1, d8), (a89, b3, c1, d9), (a89, b3, c1, d10), (a89, b3, c1,d11), (a89, b3, c1, d12), (a89, b3, c1, d13), (a89, b3, c1, d14), (a89,b3, c1, d15), (a89, b3, c1, d6), (a89, b3, c1, d17), (a89, b3, c1, d18),(a89, b3, c1, d19), (a89, b3, c1, d20), (a89, b3, c1, d21), (a89, b3,c1, d22), (a89, b3, c2, d1), (a89, b3, c2, d2), (a89, b3, c2, d3), (a89,b3, c2, d4), (a89, b3, c2, d5), (a89, b3, c2, d6), (a89, b3, c2, d7),(a89, b3, c2, d8), (a89, b3, c2, d9), (a89, b3, c2, d10), (a89, b3, c2,d11), (a89, b3, c2, d12), (a89, b3, c2, d13), (a89, b3, c2, d14), (a89,b3, c2, d15), (a89, b3, c2, d16), (a89, b3, c2, d17), (a89, b3, c2,d18), (a89, b3, c2, d19), (a89, b3, c2, d20), (a89, b3, c2, d21), (a89,b3, c2, d22), (a89, b3, c3, d11), (a89, b3, c3, d2), (a89, b3, c3, d3),(a89, b3, c3, d4), (a89, b3, c3, d5), (a89, b3, c3, d6), (a39, b3, c3,d7), (a39, b3, c3, d8), (a89, b3, c3, d9), (a89, b3, c3, d10), (a89, b3,c3, d11), (a89, b3, c3, d12), (a89, b3, c3, d13), (a39, b3, c3, d14),(a89, b3, c3, d15), (a89, b3, c3, d16), (a89, b3, c3, d17), (a89, b3,c3, d18), (a89, b3, c3, d19), (a89, b3, c3, d20), (a89, b3, c3, d21),(a89, b3, c3, d22), (a89, b4, c1, d1), (a89, b4, c1, d2), (a89, b4, c1,d3), (a89, b4, c1, d4), (a88, b4, c1, d5), (a89, b4, c1, d6), (a89, b4,c1, d7), (a89, b4, c1, d8), (a89, b4, c1, d9), (a89, b4, c1, d10), (a89,b4, c1, d11), (a89, b4, c1, d12), (a89, b4, c1, d13), (a89, b4, c1,d14), (a88, b4, c1, d15), (a89, b4, c1, d16), (a89, b4, c1, d17), (a89,b4, c1, d18), (a89, b4, c1, d19), (a89, b4, c1, d20), (a89, b4, c1,d21), (a89, b4, c1, d22), (a89, b4, c2, d1), (a89, b4, c2, d2), (a89,b4, c2, d3), (a89, b4, c2, d4), (a89, b4, c2, d5), (a89, b4, c2, d6),(a89, b4, c2, d7), (a89, b4, c2, d8), (a88, b4, c2, d9), (a39, b4, c2,d10), (a89, b4, c2, d11), (a89, b4, c2, d12), (a89, b4, c2, d13), (a89,b4, c2, d14), (a89, b4, c2, d15), (a89, b4, c2, d16), (a89, b4, c2,d17), (a89, b4, c2, d18), (a39, b4, c2, d19), (a89, b4, c2, d20), (a89,b4, c2, d21), (a89, b4, c2, d22), (a89, b4, c3, d1), (a89, b4, c3, d2),(a89, b4, c3, d3), (a89, b4, c3, d4), (a89, b4, c3, d5), (a89, b4, c3,d6), (a89, b4, c3, d7), (a89, b4, c3, d8), (a89, b4, c3, d9), (a89, b4,c3, d10), (a88, b4, c3, d11), (a89, b4, c3, d12), (a89, b4, c3, d13),(a89, b4, c3, d14), (a89, b4, c3, d15), (a89, b4, c3, d16), (a89, b4,c3, d17), (a89, b4, c3, d18), (a89, b4, c3, d19), (a88, b4, c3, d20),(a39, b4, c3, d21), (a89, b4, c3, d22), (a89, b5, c1, d1), (a89, b5, c1,d2), (a89, b5, c1, d3), (a89, b5, c1, d4), (a89, b5, c1, d5), (a89, b5,c1, d6), (a89, b5, c1, d7), (a89, b5, c1, d8), (a89, b5, c1, d9), (a89,b5, c1, d10), (a89, b5, c1, d11), (a89, b5, c1, d12), (a89, b5, c1,d13), (a89, b5, c1, d14), (a89, b5, c1, d15), (a89, b5, c1, d16), (a89,b5, c1, d17), (a89, b5, c1, d18), (a89, b5, c1, d19), (a89, b5, c1,d20), (a89, b5, c1, d21), (a89, b5, c1, d22), (a89, b5, c2, d1), (a89,b5, c2, d2), (a89, b5, c2, d3), (a89, b5, c2, d4), (a89, b5, c2, d5),(a89, b5, c2, d6), (a89, b5, c2, d7), (a89, b5, c2, d8), (a89, b5, c2,d9), (a89, b5, c2, d10), (a89, b5, c2, d11), (a89, b5, c2, d12), (a89,b5, c2, d13), (a89, b5, c2, d14), (a89, b5, (c2, d15), (a89, b5, c2,d16), (a89, b5, c2, d17), (a89, b5, c2, d18), (a89, b5, c2, d19), (a89,b5, c2, d20), (a89, b5, c2, d21), (a89, b5, c2, d22), (a89, b5, c3, d1),(a89, b5, c3, d2), (a89, b5, c3, d3), (a89, b5, c3, d4), (a89, b5, c3,d5), (a89, b5, c3, d6), (a89, b5, c3, d7), (a89, b5, c3, d5), (a89, b5,c3, d9), (a89, b5, c3, d10), (a39, b5, c3, d11), (a89, b5, c3, d12),(a88, b5, c3, d13), (a89, b5, c3, d14), (a39, b5, c3, d15), (a89, b5,c3, d16), (a39, b5, c3, d17), (a89, b5, c3, d18), (a89, b5, c3, d19),(a89, b5, c3, d20), (a89, b5, c3, d21), (a89, b5, c3, d22), (a89, b6,c1, d1), (a89, b6, c1, d12), (a89, b6, c1, d3), (a89, b6, c1, d4), (a89,b6, c1, d5), (a89, b6, c1, d6), (a89, b6, c1, d7), (a89, b6, c1, d8),(a89, b6, c1, d9), (a89, b6, c1, d10), (a89, b6, c1, d11), (a89, b6, c1,d12, (a89, b6, c1, d13), (a89, b6, c1, d14), (a89, b6, c1, d15), (a89,b1, c1, d16), (a89, b1, c1, d17), (a89, b1, c1, d18), (a89, b1, c1,d19), (a89, b1, c1, d20), (a89, b6, c1, d21), (a89, b6, c1, d22), (a89,b6, c2, d1), (a89, b6, c2, d2), (a89, b6, c2, d3), (a89, b6, c2, d4,(a89, b6, c2, d5), (a89, b6, c2, d6), (a89, b6, c2, d7), (a89, b6, c2,d8), (a89, b6, c2, d9), (a89, b6, c2, d10), (a89, b6, c2, d11), (a89,b6, c2, d12), (a89, b6, c2, d13), (a89, b6, c2, d14), (a89, b6, c2,d15), (a89, b6, c2, d16), (a89, b6, c2, d17), (a89, b6, c2, d18), (a89,b6, c2, d19), (a89, b6, c2, d20), (a89, b6, c2, d21), (a89, b6, c2,d22), (a89, b6, c3, d1), (a89, b6, c3, d2), (a89, b6, c3, d3), (a89, b6,c3, d4), (a89, b6, c3, d5), (a89, b6, c3, d6), (a89, b6, c3, d7), (a89,b6, c3, d8), (a89, b6, c3, d9), (a89, b6, c3, d10), (a89, b6, c3, d11),(a89, b6, c3, d12), (a89, b6, c3, d13), (a89, b6, c3, d14), (a89, b6,c3, d15), (a89, b6, c3, d16), (a89, b6, c3, d17), (a89, b6, c3, d18),(a89, b6, c3, d19), (a89, b6, c3, d20), (a89, b6, c3, d21), (a89, b6,c3, d22), (a90, b1, c1, d1), (a90, b1, c1, d2), (a90, b1, c1, d3), (a90,b1, c1, d4), (a90, b1, c1, d5), (a90, b1, c1, d6), (a90, b1, c1, d7),(a90, b1, c1, d8), (a90, b1, c1, d9), (a90, b1, c1, d10), (a90, b1, c1,d11), (a90, b1, c1, d12), (a90, b1, c1, d13), (a90, b1, c1, d14), (a90,b1, c1, d15), (a90, b1, c1, d16), (a90, b1, c1, d17), (a90, b1, c1,d18), (a90, b1, c1, d19), (a90, b1, c1, d20), (a90, b1, c1, d21), (a90,b1, c1, d22), (a90, b1, c2, d1), (a90, b1, c2, d2), (a90, b1, c2, d3),(a90, b1, c2, d4), (a90, b1, c2, d5), (a90, b1, c2, d6), (a90, b1, c2,d7), (a90, b1, c2, d8), (a90, b1, c2, d9), (a90, b1, c2, d10), (a90, b1,c2, d11), (a90, b1, c2, d12), (a90, b1, c2, d13), (a90, b1, c2, d14),(a90, b1, c2, d15), (a90, b1, c2, d16), (a90, b, c2, d17), (a90, b1, c2,d18), (a90, b1, c2, d19), (a90, b1, c2, d20), (a90, b1, c2, d21), (a90,b1, c2, d22), (a90, b1, c3, d1), (a90, b1, c3, d2), (a90, b1, c3, d3),(a90, b1, c3, d4), (a90, b1, c3, d5), (a90, b1, c3, d6), (a90, b1, c3,d7), (a90, b1, c3, d8), (a90, b1, c3, d9), (a90, b1, c3, d10), (a90, b1,c3, d11), (a90, b1, c3, d12), (a90, b1, c3, d13), (a90, b1, c3, d14),(a90, b1, c3, d15), (a90, b1, c3, d16), (a90, b, c3, d17), (a90, b1, c3,d18), (a90, b1, c3, d19), (a90, b1, c3, d20), (a90, b1, c3, d21), (a90,b1, c3, d22), (a90, b2, c1, d1), (a90, b2, c1, d2), (a90, b2, c1, d3),(a90, b2, c1, d4), (a90, b2, c1, d5), (a90, b2, c1, d6), (a90, b2, c1,d7), (a90, b2, c1, d8), (a90, b2, c1, d9), (a90, b2, c1, d10), (a90, b2,c1, d11), (a90, b2, c1, d12), (a90, b2, c1, d13), (a90, b2, c1, d14),(a90, b2, c1, d15), (a90, b2, c1, d16), (a90, b2, c1, d17), (a90, b2,c., d18), (a90, b2, c1, d19), (a90, b2, c1, d20), (a90, b2, c1, d21),(a90, b2, c1, d22), (a90, b2, c2, d1), (a90, b2, c2, d2), (a90, b2, c2,d3), (a90, b2, c2, d4), (a90, b2, c2, d5), (a90, b2, c2, d6), (a90, b2,c2, d7), (a90, b2, c2, d8), (a90, b2, c2, d9), (a90, b2, c2, d10), (a90,b2, c2, d11), (a90, b2, c2, d12), (a90, b2, c2, d13), (a90, b2, c2,d14), (a90, b2, c2, d15), (a90, b2, c2, d16), (a90, b2, c2, d17), (a90,b2, c2, d18), (a90, b2, c2, d19), (a90, b2, c2, d20), (a90, b2, c2,d21), (a90, b2, c2, d22), (a90, b2, c3, d1), (a90, b2, c3, d2), (a90,b2, c3, d3), (a90, b2, c3, d4), (a90, b2, c3, d5), (a90, b2, c3, d16),(a90, b2, c3, d7), (a90, b2, c3, d8), (a90, b2, c3, d9), (a90, b2, c3,d10), (a90, b2, c3, d11), (a90, b2, c3, d12), (a90, b2, c3, d13), (a90,b2, c3, d14), (a90, b2, c3, d15), (a90, b2, c3, d16), (a90, b2, c3,d17), (a90, b2, c3, d18), (a90, b2, c3, d19), (a90, b2, c3, d20), (a90,b2, c3, d21), (a90, b2, c3, d22), (a90, b3, c1, d1), (a90, b3, c1, d2),(a90, b3, c1, d3), (a90, b3, c1, d4), (a90, b3, c1, d5), (a90, b3, c1,d16), (a90, b3, c1, d7), (a90, b3, c1, d8), (a90, b3, c1, d9), (a90, b3,c1, d10), (a90, b3, c1, d11), (a90, b3, c1, d12), (a90, b3, c1, d13),(a90, b3, c1, d14), (a90, b3, c1, d15), (a90, b3, c1, d16), (a90, b3,c1, d17), (a90, b3, c1, d18), (a90, b3, c1, d19), (a90, b3, c1, d20),(a90, b3, c1, d21), (a90, b3, c1, d22), (a90, b3, c2, d1), (a90, b3, c2,d2), (a90, b3, c2, d13), (a90, b3, c2, d4), (a90, b3, c2, d5), (a90, b3,c2, d6), (a90, b3, c2, d7), (a90, b3, c2, d3), (a90, b3, c2, d9), (a90,b3, c2, d10), (a90, b3, c2, d11), (a90, b3, c2, d12), (a90, b3, c2,d13), (a90, b3, c2, d14), (a90, b3, c2, d15), (a90, b3, c2, d16), (a90,b3, c2, d17), (a90, b3, c2, d18), (a90, b3, c2, d19), (a90, b3, c2,d20), (a90, b3, c2, d21), (a90, b3, c2, d22), (a90, b3, c3, d1), (a90,b3, c3, d2), (a90, b3, c3, d3), (a90, b3, c3, d4), (a90, b3, c3, d5),(a90, b3, c3, d6), (a90, b3, c3, d7), (a90, b3, c3, d8), (a90, b3, c3,d9), (a90, b3, c3, d10), (a90, b3, c3, d11), (a90, b3, c3, d12), (a90,b3, c3, d13), (a90, b3, c3, d14), (a90, b3, c3, d15), (a90, b3, c3,d16), (a90, b3, c3, d17), (a90, b3, c3, d18), (a90, b3, c3, d19), (a90,b3, c3, d20), (a90, b3, c3, d21), (a90, b3, c3, d22), (a90, b4, c1, d1),(a90, b4, c1, d2), (a90, b4, c1, d3), (a90, b4, c1, d4), (a90, b4, c1,d5), (a90, b4, c1, d6), (a90, b4, c1, d7), (a90, b4, c1, d8), (a90, b4,c1, d9), (a90, b4, c1, d10), (a90, b4, c1, d11), (a90, b4, c1, d12),(a90, b4, c1, d13), (a90, b4, c1, d14), (a90, b4, c1, d15), (a90, b4,c1, d16), (a90, b4, c1, d17), (a90, b4, c1, d18), (a90, b4, c1, d19),(a90, b4, c1, d20), (a90, b4, c1, d21), (a90, b4, c1, d22), (a90, b4,c2, d1), (a90, b4, c2, d2), (a90, b4, c2, d3), (a90, b4, c2, d4), (a90,b4, c2, d5), (a90, b4, c2, d6), (a90, b4, c2, d7), (a90, b4, c2, d8),(a90, b4, c2, d9), (a90, b4, c2, d10), (a90, b4, c2, d11), (a90, b4, c2,d12), (a90, b4, c2, d13), (a90, b4, c2, d14), (a90, b4, c2, d15), (a90,b4, c2, d16), (a90, b4, c2, d17), (a90, b4, c2, d18), (a90, b4, c2,d19), (a90, b4, c2, d20), (a90, b4, c2, d21), (a90, b4, c2, d22), (a90,b4, c3, d1), (a90, b4, c3, d2), (a90, b4, c3, d3), (a90, b4, c3, d4),(a90, b4, c3, d5), (a90, b4, c3, d6), (a90, b4, c3, d7), (a90, b4, c3,d8), (a90, b4, c3, d9), (a90, b4, c3, d10), (a90, b4, c3, d11), (a90,b4, c3, d12), (a90, b4, c3, d13), (a90, b4, c3, d14), (a90, b4, c3,d15), (a90, b4, c3, d16), (a90, b4, c3, d17), (a90, b4, c3, d18), (a90,b4, c3, d19), (a90, b4, c3, d20), (a90, b4, c3, d21), (a90, b4, c3,d22), (a90, b5, c1, d1), (a90, b5, c1, d2), (a90, b5, c1, d3), (a90, b5,c1, d4), (a90, b5, c1, d5), (a90, b5, c1, d6), (a90, b5, c1, d7), (a90,b5, c1, d8), (a90, b5, c1, d9), (a90, b5, c1, d10), (a90, b5, c1, d11),(a90, b5, c1, d12), (a90, b5, c1, d3), (a90, b5, c1, d14), (a90, b5, c1,d15), (a90, b5, c1, d16), (a90, b5, c1, d17), (a90, b5, c1, d18), (a90,b5, c1, d19), (a90, b5, c1, d20), (a90, b5, c1, d21), (a90, b5, c1,d22), (a90, b5, c2, d1), (a90, b5, c2, d2), (a90, b5, c2, d3), (a90, b5,c2, d4), (a90, b5, c2, d5), (a90, b5, c2, d6), (a90, b5, c2, d7), (a90,b5, c2, d8), (a90, b5, c2, d9), (a90, b5, c2, d10), (a90, b5, c2, d11),(a90, b5, c2, d12), (a90, b5, c2, d13), (a90, b5, c2, d14), (a90, b5,c2, d15), (a90, b5, c2, d16), (a90, b5, c2, d17), (a90, b5, c2, d18),(a90, b5, c2, d19), (a90, b5, c2, d20), (a90, b5, c2, d21), (a90, b5,c2, d22), (a90, b, c3, d1), (a90, b5, c3, d2), (a90, b5, c3, d3), (a90,b5, c3, d4), (a90, b5, c3, d5), (a90, b5, c3, d6), (a90, b5, c3, d7),(a90, b5, c3, d8), (a90, b5, c3, d9), (a90, b5, c3, d10), (a90, b5, c3,d11), (a90, b5, c3, d12), (a90, b5, c3, d13), (a90, b5, c3, d14), (a90,b5, c3, d15), (a90, b5, c3, d16), (a90, b5, c3, d17), (a90, b5, c3,d18), (a90, b5, c3, d19), (a90, b5, c3, d20), (a90, b5, c3, d21), (a90,b5, c3, d22), (a90, b6, c2, d1), (a90, b6, c2, d2), (a90, b6, c1, d3),(a90, b6, c1, d4), (a90, b6, c1, d5), (a90, b6, c1, d6), (a90, b6, c1,d7), (a90, b6, c1, d8), (a90, b6, c1, d9), (a90, b6, c1, d10), (a90, b6,c1, d11), (a90, b6, c1, d12), (a90, b6, c1, d13), (a90, b6, c1, d14),(a90, b6, c1, d15), (a90, b6, c1, d16), (a90, b6, c1, d17), (a90, b6,c1, d18), (a90, b6, c1, d19), (a90, b6, c1, d20), (a90, b6, c1, d21),(a90, b6, c1, d22), (a90, b6, c2, d1), (a90, b6, c2, d2), (a90, b6, c2,d3), (a90, b6, c2, d4), (a90, b6, c2, d5), (a90, b6, c2, d6), (a90, b6,c2, d7), (a90, b6, c2, d8), (a90, b6, c2, d9), (a90, b6, c2, d10), (a90,b6, c2, d11), (a90, b6, c2, d12), (a90, b6, c2, d13), (a90, b6, c2,d14), (a90, b6, c2, d15), (a90, b6, c2, d16), (a90, b6, c2, d17), (a90,b6, c2, d18), (a90, b6, c2, d19), (a90, b6, c2, d20), (a90, b6, c2,d21), (a90, b6, c2, d22), (a90, b6, c3, d1), (a90, b6, c3, d2), (a90,b6, c3, d3), (a90, b6, c3, d4), (a90, b6, c3, d5), (a90, b6, c3, d6),(a90, b6, c3, d7), (a90, b6, c3, d8), (a90, b6, c3, d9), (a90, b6, c3,d10), (a90, b6, c3, d11), (a90, b6, c3, d12), (a90, b6, c3, d3), (a90,b6, c3, d14), (a90, b6, c3, d15), (a90, b6, c3, d16), (a90, b6, c3,d17), (a90, b6, c3, d18), (a90, b6, c3, d19), (a90, b6, c3, d20), (a90,b6, c3, d21), (a90, b6, c3, d22)

The compound represented by the general formula (A) includes an opticalisomer thereof and a racemate thereof.

Test Example 1 Enzyme Inhibitory Activity of Test Compound on EGFR andHER2

EGFR and HER2 purified from an insect cell expression system, and abiotinylated substrate (synthetic peptide of glutamic acid:tyrosine=4:1)were added to a 384-well plate with ATP added thereto, and an enzymereaction was performed at room temperature. After completion of theenzyme reaction, an anti-phosphorylated tyrosine antibody labeled witheuropium and streptavidin labeled with alphycocyanine were added, and aphosphorylated tyrosine residue was quantified by a time resolutionfluorescence method.

(Preparation of Test Compound)

A test compound was adjusted to 10 mM using DMSO.

Further, using 10% DMSO solution, a 1 mM solution was prepared, and thiswas regarded as a maximum concentration point.

As a dilution series, a 4-fold dilution series was prepared to a 10stage.

(Reagent Preparation)

Preparation of Buffer:

As a buffer, TBS containing 10 mM MgCl₂, 5 mM MnCl₂, 0.2 mM Na₃VO₄, and0.1% BSA was used.

Enzyme:

As EGFR and HER2 enzymes, those purified from an insect cell expressionsystem were purchased from Carna Biosciences, Inc.

An EGFR enzyme solution was adjusted to 250 ng/ml using a buffer. HER2kinase was adjusted to 1000 ng/ml using a buffer.

Substrate Solution:

As a substrate, biotinylated poly-Glu-Tyr (4:1, manufactured by CISbio)was used. A concentration was adjusted to 3.125 μg/ml using the abovebuffer.

ATP Solution:

An ATP concentration on study of the EGFR enzyme was adjusted to 125 μMusing the buffer.

An ATP concentration on study of the HER2 enzyme was adjusted to 290 μM.

Detection Reagent:

For preparing a detection reagent, TBS containing 30 mM EDTA, 0.8M KFand 0.1% BSA was used.

An anti-phosphorylated tyrosine antibody labeled with europium, PT-66K(CISbio) was adjusted to 195 ng/ml, and streptavidin labeled withalphycocyanine, SA-XL(CISbio) was adjusted to 5 μg/ml.

(Assay Method)

As an assay plate, a 384-well plate was used. Per one well, 1.1 μl of atest compound, 4 μl of a substrate solution, and 4 μl of an enzymesolution were added, and 2 μl of an ATP solution was added to initiatean enzyme reaction. The enzyme reaction was performed at roomtemperature for 60 minutes, and 10 μl of a detection reagent was addedto complete the reaction. One hour after completion of the reaction,time resolution fluorescent measurement was performed.

(Assessment Method)

Using 10% DMSO in place of a test compound, and letting a signal ataddition of ATP to be 0% inhibition (enzyme activity 100%), and lettinga signal in the absence of ATP to be 100% inhibition (enzyme activity0%), the inhibitory activity at addition of a test compound wascalculated.

The inhibitory activity (IC₅₀ value, nM) of compounds described inExamples on EGFR and HER2 is shown below.

TABLE 50 Compound No. EGFR (nM) HER2 (nM) V-6 6.5 3.6 V-7 36 76 V-43 186151 VIII-7 103 348 VIII-10 409 484 VIII-11 43 45 VIII-12 209 227 VIII-13300 888 VIII-19 89 115 VIII-20 29 31 VIII-27 33 43 VIII-28 162 167VIII-29 102 513 VIII-32 50 46 VIII-35 11 25 VIII-40 9.3 19.2 VIII-41 1215 VIII-42 10 11 VIII-44 26 6.3 VIII-45 58 152 VIII-46 82 104 VIII-47 1223 VIII-48 44 15 VIII-49 28 31 VIII-50 19 15 VIII-51 45 64 VIII-52 19 28VIII-53 79 80 VIII-55 19 68 VIII-56 7.9 13.8 VIII-57 301 803 VIII-58 207236 VIII-59 115 278 VIII-60 54 30 VIII-61 30 24 VIII-62 22 22 VIII-639.6 9.2 VIII-64 52 88 VIII-65 97 98 VIII-66 27 43 VIII-67 16 14 VIII-6819 25 VIII-69 43 28 VIII-70 63 31 VIII-71 130 199 VIII-72 6.3 11 VIII-73275 199 VIII-74 164 150 VIII-75 50 34 VIII-76 162 216 VIII-77 217 246VIII-78 111 410 VIII-80 23 29 VIII-81 9.8 17.7 VIII-82 7.6 7.5 VIII-83164 121 VIII-84 44 47 VIII-85 32 33 VIII-86 244 304 VIII-87 642 476VIII-88 47 56 VIII-89 27 24 VIII-90 93 97 VIII-91 74 83 VIII-92 32 36VIII-93 453 321 VIII-94 213 150 VIII-95 209 176 VIII-96 20 20 VIII-97 1922 VIII-98 21 21 VIII-99 84 84 VIII-100 208 203 VIII-101 56 129 VIII-10272 121 VIII-103 3.9 5.6 VIII-104 238 202 VIII-105 14 14 VIII-106 160 148VIII-107 150 135 VIII-108 53 56 VIII-109 23 18 VIII-110 29 35 VIII-11137 55 VIII-112 11 13 VIII-113 9.7 12 VIII-114 57 69 VIII-116 37 25VIII-117 47 63 VIII-118 197 223 VIII-119 81 77 VIII-120 83 29 VIII-12117 18 VIII-122 29 24

TABLE 51 Compound No. EGFR (nM) HER2 (nM) VIII-123 24 38 VIII-124 40 38VIII-125 118 103 VIII-126 101 123 VIII-127 37 35 VIII-128 15 17 VIII-1297.1 6.8 VIII-130 8.1 5.2 VIII-131 5.8 4.4 VIII-132 14 14 VIII-133 8.47.1 VIII-134 7.1 7.4 VIII-135 7.6 8.1 VIII-136 21 21 VIII-137 13 14VIII-139 5 3.8 VIII-140 5.5 4.3 VIII-141 10 7.9 VIII-142 5.5 4.4VIII-143 3.5 3.6 VIII-145 9.4 8.9 VIII-146 12 10 VIII-147 13 13 VIII-1486.1 5.8 VIII-149 13 14 VIII-150 12 11 VIII-151 20 10 VIII-152 2.4 4.3VIII-153 10 11 VIII-154 9.5 9 VIII-155 10 8 VIII-156 7 6.4 VIII-157 4.14 VIII-158 3.8 3.8 VIII-159 16 19 VIII-160 17 18 VIII-161 14 15 VIII-16251 62 VIII-163 23 27 VIII-164 7.3 7.6 VIII-165 11 11 VIII-167 4.8 4.2VIII-168 8 9 VIII-169 13 15 VIII-170 5 5.6 VIII-171 9.9 11.7 VIII-172 1416 VIII-173 4.8 3.9 VIII-174 25 28 VIII-176 23 26 VIII-177 7.3 5.8VIII-178 8.1 8.2 VIII-179 4.6 5 VIII-180 7.8 6 VIII-181 6.2 5.9 VIII-1824.7 7.3 VIII-183 7.1 8.3 VIII-184 10 7 VIII-185 6.8 12.5 VIII-186 19 26VIII-187 10 9 VIII-188 20 30 VIII-189 17 27 VIII-190 8.9 11.1 VIII-19117 42 VIII-192 6.2 14.2 VIII-193 14 15 VIII-194 8.6 13 VIII-195 45 43VIII-196 11 20 VIII-197 9 21 VIII-198 3.6 4.6 VIII-199 6.3 5.2 VIII-2009.7 9.6 VIII-205 17 13 VIII-207 21 17 VIII-208 28 23 VIII-209 38 30VIII-210 42 14 VIII-211 23 18 VIII-213 18 25 VIII-214 4.5 3.3 VIII-21622 7 VIII-218 76 22 VIII-219 26 20 VIII-220 263 449 VIII-221 143 168VIII-223 253 217 VIII-224 122 118 VIII-225 47 70 VIII-226 20 10 IX-1 138203 IX-4 193 334 IX-6 344 326 IX-8 426 549

Test Example 2 Test of In Vitro Cell Proliferation Inhibition of TestCompound

As a human-derived cancer cell strain, BT-474 was used. Cells were allcultured in a 37° C., 5% CO₂ incubator in a medium in which 1.0% bovinefetal serum (ICN) and 50 units ml penicillin/50 μg/ml streptomycinsolution (GIBCO) were added to Dulbecco's Modified Essential Medium(DMEM, Nacalai Tesque, Inc). Each 3000/well of cells were seeded on a96-well plate (Sumitomo Bakelite Co., Ltd.) and, on the next day, a drugwas added to a maximum concentration of 3×10⁻¹⁰ to 10⁻⁵ M. Aftercultured for 3 days, WST (water-soluble tetrazolium salt) assay wasperformed, and an IC₅₀ value was calculated.

The proliferation inhibitory activity (IC₅₀ value, nM) of compoundsdescribed in Examples on BT-474 is shown below.

TABLE 52 Compound BT-474 No. (nM) V-6 110 V-7 134 V-43 71 VIII-7 63VIII-10 27 VIII-11 26 VIII-12 69 VIII-13 64 VIII-20 37 VIII-27 13VIII-28 72 VIII-29 77 VIII-32 32 VIII-35 24 VIII-40 9 VIII-41 14 VIII-4224 VIII-44 28 VIII-45 13 VIII-46 12 VIII-47 4 VIII-48 28 VIII-49 28VIII-50 27 VIII-51 9 VIII-52 9 VIII-53 12 VIII-55 25 VIII-56 14 VIII-5715 VIII-58 37 VIII-59 11 VIII-60 14 VIII-61 11 VIII-62 12 VIII-63 13VIII-64 22 VIII-65 30 VIII-66 8 VIII-67 32 VIII-68 41 VIII-69 16 VIII-707 VIII-71 17 VIII-72 21 VIII-73 12 VIII-74 28 VIII-75 22 VIII-76 12VIII-77 11 VIII-78 35 VIII-80 35 VIII-81 8 VIII-82 16 VIII-83 13 VIII-8428 VIII-85 11 VIII-86 13 VIII-87 6 VIII-88 12 VIII-89 25 VIII-90 9VIII-91 24 VIII-92 29 VIII-93 38 VIII-94 26 VIII-95 25 VIII-96 30VIII-97 11 VIII-98 65 VIII-99 24 VIII-100 16 VIII-101 12 VIII-102 7VIII-103 11 VIII-104 60 VIII-105 10 VIII-106 16 VIII-107 23 VIII-108 31VIII-109 40 VIII-110 21 VIII-111 15 VIII-112 8 VIII-113 13 VIII-114 37VIII-116 50 VIII-117 20 VIII-118 22 VIII-119 31 VIII-120 32 VIII-121 10VIII-122 14 VIII-123 31 VIII-124 14 VIII-125 10 VIII-126 9 VIII-127 61VIII-128 37 VIII-129 12 VIII-130 50 VIII-131 14 VIII-132 18 VIII-133 43VIII-134 14 VIII-135 28 VIII-136 53 VIII-137 78 VIII-139 32 VIII-140 30VIII-141 46 VIII-142 31 VIII-143 24 VIII-145 21 VIII-146 45 VIII-147 25VIII-148 26 VIII-149 28 VIII-150 30 VIII-151 47 VIII-152 22 VIII-153 21VIII-154 31 VIII-155 28 VIII-156 24 VIII-157 25 VIII-158 27 VIII-159 15VIII-160 47 VIII-161 49 VIII-162 42 VIII-163 38 VIII-164 31 VIII-165 23VIII-167 21 VIII-168 44 VIII-169 35 VIII-170 19 VIII-171 52 VIII-172 70VIII-173 40

TABLE 53 Compound BT-474 No. (nM) VIII-174 14 VIII-176 26 VIII-177 79VIII-178 36 VIII-179 48 VIII-180 5 VIII-181 13 VIII-182 20 VIII-183 10VIII-184 9 VIII-185 12 VIII-186 29 VIII-187 24 VIII-188 40 VIII-189 25VIII-190 14 VIII-191 33 VIII-192 24 VIII-193 25 VIII-194 25 VIII-195 29VIII-196 28 VIII-197 14 VIII-198 10 VIII-199 33 VIII-200 8 VIII-205 31VIII-207 68 VIII-208 27 VIII-209 19 VIII-210 31 VIII-211 16 VIII-213 33VIII-214 25 VIII-216 32 VIII-218 41 VIII-219 45 VIII-220 23 VIII-221 15VIII-223 6 VIII-224 1.2 VIII-225 7 VIII-226 5

Test Example 3 Assessment Test of In Vivo Anti-tumor of Test Compound

NCI-N87 cells (human stomach cancer cell strain) were transplanted intoa mammary fat pad of a female nude mouse (BALB/cA Jcl-nu/nu, CLEA Japan,Inc) at 5×10⁶ cells/mouse (day 0). On day 5, a long diameter and a shortdiameter of a tumor were measured with a caliper, and mice were dividedinto groups (N=6) so that a tumor size between groups became equal. Atest compound (20, 80 mg/kg) suspended in a 0.5% methylcellulose (MC)solution was orally administered from day 5 on for 1.5 consecutive days,and the anti-tumor effect was expressed by a ratio (T/C %) of an averagevalue of a tumor size between a compound-administered group (T) and acontrol (C, 0.5% MC) group on day 20.

Results of in vivo anti-tumor assessment of a compound VIII-11 are shownin Table 54, and results of in vivo anti-tumor assessment of a compoundVIII-66 are shown in Table 55.

TABLE 54 Mean of tumor size Control 20 mg/kg 80 mg/kg (mm³) groupadministrated group administrated group day 5 192 197 197 day 20 655 356193 T/C % 100% 54% 29%

TABLE 55 Mean of tumor size Control 20 mg/kg 80 mg/kg (mm³) groupadministrated group administrated group day 5 150 134 150 day 20 483 15417 T/C % 100% 32% 4%

Preparation Examples Preparation Example 1

A granule containing the following ingredient is prepared.

Ingredient Compound represented by the formula (I)  10 mg Lactose 700 mgCorn starch 274 mg HPC-L  16 mg 1000 mg 

The compound represented by the formula (I) and lactose are passedthrough a 60 mesh sieve. Corn starch is passed through a 1.20 meshsieve. These are mixed with a V-type mixing machine. An aqueous solutionof HPC-L (low viscosity hydroxypropylcellulose) is added to a mixturepowder, and this is kneaded, granulated (extrusion granulation, porediameter 0.5 to 1 mm), and dried. The resulting dry granule is sievedwith a vibration sieve (12/60 mesh) to obtain a granule.

Preparation Example 2

A powder for filling into a capsule containing the following ingredientsis prepared.

Ingredient Compound represented by the formula (I) 10 mg Lactose 79 mgCorn starch 10 mg Magnesium stearate  1 mg 100 mg 

The compound represented by the formula (I), and lactose are passedthrough a 60 mesh sieve. Corn starch is passed through a 120 mesh sieve.These and magnesium stearate are mixed with a V-type mixing machine. 10trituration 100 mg is filled into a No. 5 hard gelatin capsule.

Preparation Example 3

A granule for filling into a capsule containing the followingingredients is prepared.

Ingredient Compound represented by the formula (I) 15 mg Lactose 90 mgCorn starch 42 mg HPC-L  3 mg 150 mg 

The compound represented by the formula (I), and lactose are passedthrough a 60 mesh sieve. Corn starch is passed through a 120 mesh sieve.These are mixed, a HPL-L solution is added to a mixture powder, and thisis kneaded, granulated, and dried. The resulting dry granule is adjustedin a size, 150 mg of which is filled into a No. 4 hard gelatin capsule.

Preparation Example 4

A tablet containing the following ingredients is prepared.

Ingredient Compound represented by the formula (I) 10 mg Lactose 90 mgMicrocrystaline cellulose 30 mg CMC-Na 15 mg Magnesium stearate  5 mg150 mg 

The compound represented by the formula (I), lactose, microcrystallinecellulose. CMC-Na (carboxymethylcellulose sodium salt) are passedthrough a 60 mesh sieve, and mixed. Magnesium stearate is mixed into amixture powder to obtain a mixture powder for tabletting. The presentmixed powder is directly compressed to obtain a 150 mg tablet.

Preparation Example 5

An intravenous preparation is prepared as follows:

Compound represented by the formula I  100 mg Saturated fatty acidglyceride 1000 ml

A solution of the above ingredients is intravenously administered topatient at a rate of 1 ml per minute.

INDUSTRIAL APPLICABILITY

Since the present compound has the excellent action of inhibiting an EGFreceptor and HER2, and is highly safe, it is useful as a medicament,inter alia, a therapeutic for a cancer.

1. A compound represented by the general formula (I):

wherein Rx is a group represented by the formula:

wherein R¹ is a hydrogen atom, optionally substituted alkyl, optionallysubstituted alkenyl, optionally substituted aryl, or an optionallysubstituted non-aromatic nitrogen-containing heterocyclic group; Z is—O—; R² is a hydrogen atom, optionally substituted alkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted cycloalkyl, optionally substituted aryl, or optionallysubstituted heteroaryl; R³ and R⁴ are independently a hydrogen atom,optionally substituted alkyl, optionally substituted alkenyl, optionallysubstituted alkynyl, optionally substituted alkyloxy, optionallysubstituted alkenyloxy, halogen, hydroxy, mercapto, or optionallysubstituted amino; X is —O—, —S—, —N(R¹²)—, or alkylene which may beintervened with —O—, —S—, or —N(R¹³)—; R¹² and R¹³ are independently ahydrogen atom, alkyl, acyl, alkyloxycarbonyl, alkenyloxycarbonyl, oraralkyloxycarbonyl; and A is a group represented by the formula:

wherein R⁵ is a hydrogen atom, halogen, optionally substituted alkyloxy,optionally substituted alkenyloxy, optionally substituted alkynyloxy, ora group represented by the formula: —Y—R⁸ wherein Y is —O—, —S—, —SO₂—,or alkylene which may be intervened with —O—, —S—, or —N(R⁹)—; R⁸ isoptionally substituted aryl or optionally substituted heteroaryl; R⁹ isa hydrogen atom, alkyl, acyl, alkyloxycarbonyl, alkenyloxycarbonyl, oraralkyloxycarbonyl; R⁶ and R⁷ are independently a hydrogen atom,optionally substituted alkyl, optionally substituted alkenyl, optionallysubstituted alkynyl, optionally substituted alkyloxy, optionallysubstituted alkenyloxy, optionally substituted alkynyloxy, halogen,hydroxy, mercapto, cyano, or optionally substituted amino; R²⁰ isoptionally substituted alkyl, optionally substituted alkenyl, optionallysubstituted alkynyl, or a group represented by the formula:

wherein R⁵, R⁶ and R⁷ are as defined above; Q is N or CH, wherein thearyl is selected from the group consisting of phenyl, 1-naphthyl,2-naphthyl and anthryl, wherein the heteroaryl is selected from thegroup consisting of pyrrolyl, furyl, thienyl, imidazolyl, pyrazolyl,isothiazolyl, isooxazolyl, oxazolyl, thiazolyl, pyridyl, pyrazinyl,pyrimidinyl, pyridazinyl, triazolyl, tetrazolyl, oxadiazolyl,thiadiazolyl, indolydinyl, isoindolyl, indolyl, indazolyl, purinyl,quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl,quinolanyl, quinazolinyl, cinnolinyl, pteridinyl, carbazolyl,phenanthridinyl, acridinyl, dibenzofuranyl, benzoimidazolyl,benzoisooxazolyl, benzooxazolyl, benzooxadiazolyl, benzoisothiazolyl,benzothiazolyl, benzofuryl, benzothienyl,4,5-dihydronaphtho[1,2-d]thiazolyl, 4H-chromeno[4,3-d]thiazolyl,4H-thiochromeno[4,3-d]thiazolyl, 4,5-dihydrothiazolo[5,4-c]quinolyl,8H-indeno[1,2-d]thiazolyl, and5,6-dihydro-4H-3-thia-1-aza-benzo[e]azulenyl, wherein the non-aromaticheterocyclic group is selected from the group consisting ofpyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl,pyrazolinyl, piperidyl, piperazinyl, indolinyl, isoindolinyl,morpholinyl, tetrahydrofuranyl, dihydropyranyl, tetrahydropyranyl,dioxolanyl, tetrahydrothienyl, dihydrothiopyranyl,tetrahydrothiofuranyl, decahydroisoquinolinyl, azepinyl, oxepinyl,dihydrooxepinyl, tetrahydrooxepinyl, oxepanyl,4,5,6,7-tetrahydrothieno[3,2]pyridyl,2-oxa-5-aza-bicyclo[2.2.1]hepta-5-yl, andhexahydropyrazyl[2.1-b][1,3]ozadin8-yl, wherein the non-aromaticnitrogen-containing heterocyclic group is selected from the groupconsisting of azetidinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl,imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl,indolinyl, isoindolinyl, morpholinyl, 1,4-thiazinyl, thiomorpholinyl,decahydroisoquinolyl, azepinyl, diazepinyl,4,5,6,7-tetrahydrothieno[3,2]pyridyl,2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl, andhexahydropyrazyl[2.1b][1,3]oxazin-8-yl, wherein a substituent of theoptionally substituted aryl, the optionally substituted heteroaryl andthe optionally substituted non-aromatic heterocylic group is selectedfrom the group consisting of optionally substituted alkyl (as asubstituent, halogen, hydroxy, nitro, cyano, carboxy, alkyloxy,alkyloxycarbonyl or acyl), cycloalkyl, alkenyl, alkynyl, hydroxy,alkyloxy, aralkyloxy, mercapto, alkylthio, halogen, nitro, cyano,carboxy, alkyloxycarbonyl, aryloxycarbonyl, haloalkyl, haloalkyloxy,optionally substituted amino, optionally substituted aminocarbonyl,acyl, acyloxy, optionally substituted aryl (as a substituent, halogen,hydroxy, nitro, cyano, carboxy, alkyloxy, alkyloxycarbonyl or acyl),optionally substituted heteroaryl (as a substituent, halogen, hydroxy,nitro, cyano, carboxy, alkyloxy, alkyloxycarbonyl or acyl), anoptionally substituted non-aromatic heterocyclic group (as asubstituent, halogen, hydroxy, nitro, cyano, carboxy, alkyloxy,alkyloxycarbonyl or acyl), optionally substituted aralkyl (as asubstituent, halogen, hydroxy, nitro, cyano, carboxy, alkyloxy,alkyloxycarbonyl or acyl), alkylsulfonyl, guanidino, an azo group, —N═N(optionally substituted phenyl), and optionally substituted ureido, andwherein a substituent of the optionally substituted non-aromaticnitrogen-containing heterocyclic group is selected from the groupconsisting of alkyloxycarbonyl, aminocarbonyl, optionally substitutedwith a substituent selected from substituent group G consisting ofalkyl, alkenyl, and aralkyl, cyano, alkyl optionally substituted with asubstituent selected from substituent group M consisting of cyano,hydroxy, carboxy, aminocarbonyl, alkyloxycarbonyl, and alkyloxy,alkylsulfonyl, alkylsulfonylalkylcarbonyl, cycloalkyl, hydroxy,alkyloxy, mercapto, alkylthio, halogen, nitro, carboxy, haloalkyl, haloalkyloxy, acyl, acyloxy, aryl, aryloxy, aralkyl, aralkyloxy, anon-aromatic nitrogen-containing heterocyclic group, alkylcarbonylamino,aminocarbonyloxy, optionally substituted amino, oxo, guanidino, an azogroup, and optionally substituted ureido, or its pharmaceuticallyacceptable salt.
 2. The compound according to claim 1, wherein R¹ isalkyl optionally substituted with a substituent selected fromsubstituent group A consisting of hydroxy, heteroaryl, carboxy,optionally substituted amino, an optionally substituted non-aromaticnitrogen-containing heterocyclic group, optionally substitutedaminocarbonyl, and optionally substituted non-aromaticnitrogen-containing heterocyclic carbonyl, or a non-aromaticnitrogen-containing heterocyclic group optionally substituted with asubstituent selected from a substituent group B consisting ofalkyloxycarbonyl, optionally substituted aminocarbonyl, oxo, amino,carboxy, cyano, cyanoalkyl, hydroxyalkyl, alkylcarbonylamino,alkylsulfonylamino, and aminocarbonylalkyl; or its pharmaceuticallyacceptable salt.
 3. The compound according to claim 1, wherein R¹ isalkyl substituted with amino optionally substituted with a substituentselected from a substituent group C consisting of alkyl, alkenyl,alkynyl, optionally substituted aryl, araklyl, alkyloxy, hydroxyalkyl,hydroxyalkyloxyalkyl, haloalkyl, aminoalkyl optionally substituted with1 or 2 alkyl(s), alkylsulfonyl, alklysulfonylalkyl, alkylcarbonyloptionally substituted with halogen or alkyloxy, alkyloxycarbonyl,optionally substituted cycloalkyl, carboxyalkyl, optionally substitutedaminocarbonylalkyl, optionally substituted aminocarbonyloxyalkyl,alkyloxyalkyl, alkylthioalkyl, alkylcarbonylaminoalkyl,alkylsulfonylaminoalkyl, alkylsulfonyl(alkyl)aminoalkyl,alkyloxycarbonylalkyl, alkylthio(hydroxy)alkyl, cycloalkylalkyl,cyanoalkyl, optionally substituted aminoalkylcarbonyl, optionallysubstituted heteroaryl, heteroarylalkyl, hydroxyalkyloxyalkyl, anoptionally substituted non-aromatic heterocyclic group, or optionallysubstituted non-aromatic heterocyclic alkyl, alkyl substituted with anon-aromatic nitrogen-containing heterocyclic group optionallysubstituted with a substituent selected from substituent group Dconsisting of halogen; aryl; hydroxy; oxo; optionally substitutedaminocarbonyl; alkyloxycarbonyl; alkyl optionally substituted with asubstituent selected from a substituent group H consisting of optionallysubstituted aminocarbonyl, cyano, alkyloxy, alkylsulfonylamino, amino,carboxy, alkyloxycarbonyl, and hydroxy; alkylaminocarbonyl; carboxy;cyano; alkylsulfonyl; alkylcarbonyl; alkenylcarbonyl;alkylsulfonylalkylcarbonyl; alkyloxyalkylcarbonyl; alkylcarbonylamino;aminocarbonyloxy; a non-aromatic nitrogen-containing heterocyclic group;and non-aromatic heterocyclic carbonyl, or a non-aromaticnitrogen-containing heterocyclic group optionally substituted with asubstituent selected from a substituent group B consisting ofalkyloxycarbonyl, optionally substituted aminocarbonyl, oxo, amino,carboxy, cyano, cyanoalkyl, hydroxyalkyl, alkylcarbonylamino,alkylsulfonylamino, and aminocarbonylalkyl; or its pharmaceuticallyacceptable salt.
 4. The compound according to claim 1, wherein R¹⁹ isalkyl optionally substituted with a substituent selected fromsubstituent group A consisting of hydroxy, heteroaryl, carboxy,optionally substituted amino, an optionally substituted non-aromaticnitrogen-containing heterocyclic group, optionally substitutedaminocarbonyl, and optionally substituted non-aromaticnitrogen-containing heterocyclic carbonyl, aryl optionally substitutedwith a substituent selected from substituent group I consisting ofalkyloxycarbonyl, optionally substituted aminocarbonyl, cyano,cyanoalkyl, hydroxyalkyl, and aminocarbonylalkyl, or heteroaryloptionally substituted with a substituent selected from substituentgroup I, or its pharmaceutically acceptable salt.
 5. The compoundaccording to claim 1, wherein R¹⁹ is alkyl substituted with aminooptionally substituted with a substituent selected from substituentgroup C consisting of alkyl, alkenyl, alkynyl, optionally substitutedaryl, araklyl, alkyloxy, hydroxyalkyl, hydroxyalkyloxyalkyl, haloalkyl,aminoalkyl optionally substituted with 1 or 2 alkyl(s), alkylsulfonyl,alklysulfonylalkyl, alkylcarbonyl optionally substituted with halogen oralkyloxy, alkyloxycarbonyl, optionally substituted cycloalkyl,carboxyalkyl, optionally substituted aminocarbonylalkyl, optionallysubstituted aminocarbonyloxyalkyl, alkyloxyalkyl, alkylthioalkyl,alkylcarbonylaminoalkyl, alkylsulfonylaminoalkyl,alkylsulfonyl(alkyl)aminoalkyl, alkyloxycarbonylalkyl,alkylthio(hydroxy)alkyl, cycloalkylalkyl, cyanoalkyl, optionallysubstituted aminoalkylcarbonyl, optionally substituted heteroaryl,heteroarylalkyl, hydroxyalkyloxyalkyl, an optionally substitutednon-aromatic heterocyclic group, and optionally substituted non-aromaticheterocyclic alkyl, or alkyl substituted with a non-aromaticnitrogen-containing heterocyclic group optionally substituted with asubstituent selected from substituent group D consisting of halogen;aryl; hydroxy; oxo; optionally substituted aminocarbonyl;alkyloxycarbonyl; alkyl optionally substituted with a substituentselected from a substituent group H consisting of optionally substitutedaminocarbonyl, cyano, alkyloxy, alkylsulfonylamino, amino, carboxy,alkyloxycarbonyl, and hydroxy; alkylaminocarbonyl; carboxy; cyano;alkylsulfonyl; alkylcarbonyl; alkenylcarbonyl;alkylsulfonylalkylcarbonyl; alkyloxyalkylcarbonyl; alkylcarbonylamino;aminocarbonyloxy; a non-aromatic nitrogen-containing heterocyclic group;and non-aromatic heterocyclic carbonyl; or its pharmaceuticallyacceptable salt.
 6. The compound according to claim 1, wherein W¹ is agroup represented by a non-aromatic nitrogen-containing heterocyclicgroup optionally substituted with a substituent selected fromsubstituent group J consisting of alkyl, cyanoalkyl, hydroxyalkyl,aminocarbonylalkyl, alkyloxy, alkyloxycarbonyl, optionally substitutedaminocarbonyl, and cyano, or a group represented by heteroaryloptionally substituted with a substituent selected from substituentgroup J, or its pharmaceutically acceptable salt.
 7. The compoundaccording to claim 1, wherein R² is a hydrogen atom, C1-C6 alkyloptionally substituted with halogen, C2-C6 alkenyl, C2-C6 alkynyl,halogen, or phenyl, or its pharmaceutically acceptable salt.
 8. Thecompound according to claim 1, wherein one of R³ and R⁴ is a hydrogenatom, and the other is a hydrogen atom, optionally substituted alkyloxyor optionally substituted alkenyloxy, its pharmaceutically acceptablesalt.
 9. The compound according to claim 1, wherein X is —NH—, or itspharmaceutically acceptable salt.
 10. The compound according to claim 1,wherein A is a group represented by the formula:

wherein R⁵ is a hydrogen atom or halogen; R⁶ is halogen or alkynyl; andR⁷ is a hydrogen atom, or its pharmaceutically acceptable salt.
 11. Thecompound according to claim 1, wherein A is a group represented by theformula:

wherein R⁵ is alkyloxy optionally substituted with a substituentselected from substituent group E consisting of carboxy,alkoxyoxycarbonyl, cycloalkyl, and optionally substituted aminocarbonyl;alkenyloxy optionally substituted with a substituent selected fromsubstituent group E, or alkynyloxy optionally substituted with asubstituent selected from substituent group E; R⁶ is optionallysubstituted alkynyl, optionally substituted alkyloxy, or halogen; and R⁷is a hydrogen atom; or its pharmaceutically acceptable salt.
 12. Thecompound according to claim 1, wherein A is a group represented by theformula:

wherein R⁵ is a group represented by the formula: —Y—R⁸ wherein Y isalkylene which may be intervened with —O—; R⁸ is phenyl optionallysubstituted with a substituent selected from substituent group Fconsisting of halogen, carboxy, alkyl, haloalkyl, hydroxyalkyl,alkyloxy, alkyloxycarbonyl, and optionally substituted amino; pyridyloptionally substituted with a substituent selected from substituentgroup F; furyl optionally substituted with a substituent selected fromsubstituent group F; thienyl optionally substituted with a substituentselected from substituent group F; thiazolyl optionally substituted witha substituent selected from substituent group F; or oxazolyl optionallysubstituted with a substituent selected from substituent group F; R⁶ isoptionally substituted alkynyl, optionally substituted alkyloxy, orhalogen; and R⁷ is a hydrogen atom; or its pharmaceutically acceptablesalt.
 13. The compound according to claim 1, which is represented by theformula (I-Q):

wherein R⁴⁷ is a group represented by the formula:

and R³⁷ is alkyl substituted with amino optionally substituted withalkyl, hydroxyalkyl, alkylcarbonylaminoalkyl or a non-aromaticheterocyclic group; alkyl substituted with a non-aromaticnitrogen-containing heterocyclic group optionally substituted withalkyl, hydroxyalkyl, or alkylcarbonylamino; or a non-aromaticnitrogen-containing heterocyclic group substituted with hydroxyalkyl; orits pharmaceutically acceptable salt.
 14. A pharmaceutical compositioncontaining the compound as defined in claim 1 as an active ingredient.